|
ORF cDNA clones
|
CRISPR / TALEN
|
Lentivirus
|
AAV
|
TALE-TF
|
ORF knockin clones
|
|
Antibody
|
Proteins
|
miRNA target clones
|
qPCR primers
|
shRNA clones
|
miRNA products
|
Promoter clones
|
Validated All-in-One™ qPCR Primer for CDKN1A(NM_001220778.2) Search again
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Summary
This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Two alternatively spliced variants, which encode an identical protein, have been reported. [provided by RefSeq].
Gene References into function
- expression is related to apoptosis in thymus
- p21CIP1/WAF1 was able to repress the immortal phenotype. CDKIs mediate growth arrest in human osteosarcoma cell lines and provides further evidence of the existence of molecular links between cellular mortality and immortality.
- tested for inhibition of Plasmodium falciparum cyclin dependent protein kinases
- In the ovarian cancer cell lines studied, cell growth was inhibited after transfection with p16(INK4a), p21(WAF1/Cip-1), and p53.
- Cdk4 activity does correlate with changes in the level of the Cdk inhibitor p21(WAF1/Cip1
- induced after DNA damage and plays a role in cell survival
- Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia.
- The ability of p21(Cip1) to inhibit cyclin D1 nuclear export correlates with its ability to bind to Thr-286-phosphorylated cyclin D1 and thereby prevents cyclin D1.CRM1 association
- phosphorylation by AKT/PKB enhances protein stability and promotes cell survival
- expression inhibited by Hepatitis C virus core protein
- expression in normal, hyperplastic and carcinomatous human prostate
- Loss of the p21(Cip1/Waf1) cyclin kinase inhibitor results in propagation of horizontally transferred DNA.
- hinge region of the human papillomavirus type 8 E2 protein activates the human p21(WAF1/CIP1) promoter via interaction with Sp1
- We investigated three common sequence variants in TP53 and p21 for possible associations with the risk of breast cancer and with various phenotypic features of this disease
- Inhibition of bone marrow stem cell proliferation by retinol was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1).
- The onset of ATRA-induced G(0)/G(1) arrest of U-937 cells is linked to an increase in p21(WAF1/CIP1) expression.
- Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin
- Specific inhibition of p21(Waf1/Cip1) protein with the antisense oligodeoxynucleotide markedly reduces the production and secretion of the matrix proteins fibronectin and laminin, both in the presence and absence of TGF-beta stimulation.
- Early induction of CDKN1A (p21) and GADD45 mRNA by a low dose of ionizing radiation is due to their dose-dependent post-transcriptional regulation
- REVIEW: gene expression regulation and role of CDK inhibitor P21 in cell survival and cell cycle control in early hematopoiesis.
- Expression of p21WAF1 is dependent on the activation of ERK during vitamin E-succinate-induced monocytic differentiation.
- Negative regulation of cell growth and differentiation by TSG101 through association with p21(Cip1/WAF1).
- cyclooxygenase-2 inhibitor induces G0/G1 cell cycle arrest in NA cells by upregulation of p21
- expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas
- Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma.
- Results suggest that p21(Cip/WAF1) and cyclin D1 induction may result from the activation of the ERK and PI-3 kinase pathways.
- A strong inhibition of cell proliferation was observed in K562-p21(WAF1) cell as compared with that of the control, and the cell number in G(0)/G(1) phase was remarkably increased.
- interferon-alpha exerts antitumor effects by increased p21 expression in neuroendocrine tumors
- Review of the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.
- Cell attachment to the extracellular matrix induces proteasomal degradation of p21(CIP1) via Cdc42/Rac1 signaling (P21CIP1)
- H(2)O(2)-induced AP-1 activation and its effect on p21(WAF1/CIP1)-mediated G2/M arrest in a p53-deficient human lung cancer cell.
- Identification of the regulatory region required for ubiquitination of the cyclin kinase inhibitor, p21.
- Oxidized low density lipoprotein induces the cyclin-dependent kinase inhibitor p21(waf1) and the tumor suppressor Rb.
- results suggested that p21 is up-regulated by the stress of inflammation and fibrosis in hepatitis C virus (HCV)-associated chronic liver diseases and that high p21 expression might be related to hepatocarcinogenesis in cirrhotic patients
- stabilization by phosphorylation influenzed by protein kinase p38 alpha and JNK1
- p21/WAF1 expression associated with endocrine activity in pituitary adenomas; tumors expressing cytoplasmic p21/WAF1 may have resistance to DNA-damaging agents such as ionizing radiation
- P27Kip1 immunoreactivity is higher in male breast cancers compared with female breast cancers.
- transcriptional regulation of p21 CIP1 WAF1 controls p53 independent ovarian cancer apoptosis
- C/EBPalpha is essential for p21-mediated inhibition of G1 to S-phase progression by RAP in KSHV-infected host cells
- role in modulating threshold of apoptosis induced by DNA-damage and growth factor withdrawal in prostate cancer cells
- Sp1-mediated activation of p21(WAF1/CIP1) expression is accompanied by G(1) cell cycle arrest induced by 3,3'-diindolylmethane in human breast cancer cells
- inactivation sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio
- Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK.
- p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm.
- Msx2 and p21(CIP1/WAF1) mediate the proapoptotic effects of bone morphogenetic protein-4 on ventricular zone progenitor cells.
- Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation
- relationship of Mcl-1 isoforms, ratio to cyclin A and Jun kinase phosphorylation to apoptosis in human breast carcinomas
- p21(cip1) induction is interrupted by ROCK-mediated signal transduction in preapoptotic cells
- The proximal p21(WAF-1/Cip1) promoter region has been characterized and the contribution of individual Sp1 binding sites to both constitutive and inducible promoter activity in hepatocytes is analyzed in detail.
- By inhibiting p21(Cip1) expression Myc favours the initiation of apoptosis, thereby influencing the outcome of a p53 response in favour of cell death
- role of PIN1 in transactivation
- insulin inhibits TNF-alpha-dependent cell killing, induction of p53, p21 and apoptosis in a human cervical carcinoma cell line
- Forced expression of STAT5a in human cord blood-derived CD34+ cells enhanced expression Bcl-2 and p21(WAF/Cip1), suggesting they may be important in STAT5a-mediated eosinophil differentiation.
- Oxidative stress induces rapid, but reversible, downregulation of functional p21 by accelerating its protein turnover.
- In conclusion, no polymorphism exists in codon 149 of P21(Waf1/Cip1).
- Lack of p21(CIP1) DNA methylation was found in 31 patients with acute lymphocytic leukemia.
- promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1)
- The 3'-untranslated region of this protein's mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein.
- cyclin kinase inhibitors p21 are associated with laryngeal papillomas.
- LMP1 inhibits transforming growth factor-beta 1-mediated induction of MAPK/p21 in Epstein-barr virus infected gastric epithelial cell line GT38
- Hepatitis C virus NS4A and NS4B proteins at inhibited p21/Waf1 expression post-transcriptionally
- p21(waf1) has a role in aortal endothelial cell aging
- Codon 31 polymorphism is associated with bladder cancer
- WAF1 degradation is regulated by atypical PKC and PDK1
- p21(WAF1) transfection decreases sensitivity of K562 cells to VP-16
- A direct role is demonstrated for p21 in suppressing spontaneous IL-6 and MMP-1 production in rheumatoid arthritis synovial fibroblasts, whereas p21 overexpression has no effect on IL-6 or MMP-1 production in normal and osteoarthritic synovium.
- p21 expression is regulated via a mechanism that is suppressed by PP5
- p21 expression correlates positively with proliferation in oral squamous cell carcinoma. Up-regulation of p21 is associated with early progression.
- Downregulation of waf1 mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-gamma.
- repression of p21 promoter/reporters as well as the endogenous p21 gene by Myc depends on interaction with Miz-1. Expression of Miz-1 increases during hematopoietic differentiation and Miz-1 activates the p21 promoter under conditions of low Myc levels
- CDK2 activity was reduced dose-dependently after 24 h of ZD1839 treatment and this effect correlated with increased amount of p27(KIP1) and p21(CIP1/WAF1) associated with CDK2-cyclin-E and CDK2-cyclin-A complexes in head/neck squamous carcinoma cell line
- TNFalpha mediates cellular growth arrest through activation of the transcription factor NF-kappaB. The cdk inhibitor p21(Cip1/Waf1) is activated through NF-kappaB and is an important mediator of this growth arrest response
- activation by insulin-like growth factor 1 inhibits UV-induced cell death
- Gene expression is increased in chronic allograft nephropathy and coorelates with the number of acute rejection episodes.
- Upon prolonged exposure, progestins activate p53, in human breast and endometrial tumor cells, which up-regulates the p21(Cip1,Waf1) promoter.
- deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21
- Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis.
- The growth inhibitory action of ATR is associated with the activation of p21WAF1.
- These results suggest that the delay of senescence in cultures grown in the presence of dexamethasone is due to a suppression of the senescence related increase in p21(Waf1/Cip1/Sdi1).
- Egr1 controls p21Cip1 expression by directly interacting with a specific sequence on its gene promoter.
- Inhibitor shows antitumor effect on glioma cells.
- Investigations confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers.
- p21waf1/cip1 is down-regulated in the lymphocytes of rheumatoid arthritis patients.
- Mutant p53 can delay growth arrest in senescing fibroblasts without reducing p21(WAF1) expression.
- laminar flow caused an increase of p21Waf1 level in the wild-type HCT116 (p53+/+) cells but not in the p53-null HCT116 cells
- Data show that tetradecanoylphorbol acetate activated p21(WAF-1) expression by a protein kinase c-dependent mechanism and that one specific Sp1 binding site in the p21(WAF-1) promoter was critically essential for this activation.
- CDKN1A and CDKN1B variants are associated with advanced prostate cancer.
- expression of p21/CDKN1A is necessary and sufficient for the negative regulation of gene expression by p53
- Reduced expression of p21 and p27, being VDR dependent, is major pathogenic factor for nodular parathyroid gland growth in advanced secondary hyperparathyroidism. Review.
- Presence of p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21
- Histone deacetylase inhibitors activate p21(WAF1) expression via ATM.
- In carcinoma in situ without muscle-invasive disease, positive p21 expression is independently associated with bladder cancer recurrence and progression.
- The TGF-beta-1-induced decrease in CDK2 kinase activity was the result of increased p21 association with cyclin A-CDK2 and cyclin E-CDK2. , p21 induction in early G(1) is critical for TGF-beta 1 inhibition of CDK2 kinase activity.
- ErbB positive status was associated with p21 overexpression in human ductal carcinoma in situ.
- The dysfunction of p21 in NB cells represents a novel mechanism by which the G(0)-G(1) cell cycle checkpoint can be inactivated.
- p21 is highly correlated with p73 expression irrespective of the p53 mutation status in human esophageal cancers
- p21WAF1 binding to HDAC1 is disrupted by Che-1 protein in human colonic carcinoma
- p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1.
- p21(WAF1) has a role in drug-induced senescence in colorectal cancer cells
- p21CIP/WAF is a positive regulator in the cell proliferation induced by IGF-I in MCF-7 cells.
- The differences in apoptotic activity and p21(WAF1/CIP1) expression between serrated adenomas (SA) and traditional adenomas or hyperplastic polyps indicate that SA should be considered as a distinct subtype of colorectal neoplasm
- High expression of p21 Waf1 is associated with sarcoid granulomas
- Hepatitis C virus (HCV) core protein potentially modulates hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor
- p21 is required for the G1/S arrest of HCT116 colon cancer cells but its mode of action is more complicated than the simple formation of a physical complex with cyclin-Cdk2
- PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair.
- p21 has an antiapoptotic role in monocytic leukemia.
- exposure in vitro to hyperoxia exerts G(1) arrest through p53-dependent induction of p21 that suppresses Cdk and PCNA activity.
- p21WAF1/CIP1, pRB, Bax and NF-kappaB have roles in induction of growth arrest and apoptosis by resveratrol in tumor cell lines
- p21 is a transcriptional target of CDX2. Our results may thus provide a new mechanism underlying the functions of CDX2.
- UV-induced p21 degradation is essential for optimal DNA repair
- These results suggest that in vivo p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but prevents, or displaces subsequent binding of DNA polymerase delta to PCNA at the G1/S phase transition.
- the association of p21 and cyclin A in response to gamma-irradiation requires the CDK2 binding region
- Cytoplasmic p21WAFI/CIPI may be a surrogate marker of functional HER-2 in vivo.
- Resveratrol caused a dose-dependent increase in intracellular p53 and p21(WAF1/CIP1) levels.
- p21 down-regulation is multiply determined and is required for the reversibility of the arrest in S phase
- Codon 31 polymorphism in p21 may be associated with the development of esophageal cancer
- Low p21 protein level is associated with advanced TNM stage and positive nodal status of squamous cell carcinoma of hypopharyngeal cancer
- In adenocarcinomas, no statistically significant correlation was found between K-ras mutational status and p21WAF1/CIP1 and p53 expression.
- MDM2 directly inhibits p21waf1/cip1 function by reducing p21waf1/cip1 stability in a ubiquitin-independent fashion
- We conclude, therefore, that two major components of cell-cell interaction synergistically regulate cell cycle progression in HEK293 cells by regulating p21 expression in a beta-catenin/TCF-dependent manner.
- in hepatocellular carcinoma, PCNA participates both in DNA synthesis and repair and that highly proliferating cancers may display a sustained DNA-repair.
- how HO-1 and WAF1/Cip1 were regulated in two gastric cancer cell lines
- cyclin-dependent kinase inhibitor 1A (p21) levels rise abruptly in individual aging cells and remain elevated for extended periods of time.
- Promoter is hypermethylated in various lymphomas and carcinomas.
- NaB-induced apoptosis required P21(waf1/cip1) and its interaction with PCNA.
- We present evidence that p21(WAF1) is required for 9-HSA mediated growth arrest in human colon carcinoma cells
- Assessment of p21, p27, Bax, and cyclin E expression in tumor tissues have been reported to be useful as prognostic factors in head and neck squamous cell carcinoma.
- Perifosine increases Sp1 binding and enhanced p21(waf1/cip1) transcription.
- Abnormally high amounts of Stat1, Stat5 and p21Cip1 proteins were found in prehypertrophic-hypertrophic chondrocytes, the extent of overexpression being directly related to the severity of the disease
- Overexpression of integrin beta1 imposed a growth inhibitory effect on a liver neoplastic cell line which is mainly attributed to CIP1.
- by reducing p21 protein stability via proteasome-mediated degradation, MDM2 functions as a negative regulator of p21
- TGF-beta-Smad signaling pathway inhibits the growth of human epithelial cells and plays a role in tumor development.
- Loss of p21 and/or p53 might not predict for prognosis in oropharnyggeal squamous cell carcinoma.
- Transactivation of the CIP1 promotor by fetal liver kinase-3 mutations involves stat5 binding site.
- Flavopiridol abrogates depsipeptide mediated induction of p21 expression via inhibition of protein kinase C signaling in malignant pleural mesothelioma cells.
- simultaneous expression of HPV-16 E7 protein and p21 proteins induces apoptosis and activates cathepsin B
- Results suggest that basic helix-loop-helix proteins provide a direct transcriptional link between a cell cycle inhibitor, p21(Cip1), and a neurotrophic receptor, Trk.
- p21WAF1 in vascular smooth muscle cells is regulated by transcription factor Sp1 and p38MAPK
- In human colon cancer cell lines, HDAC inhibitors stimulate the p21(WAF1) gene expression by selectively increasing the degree of acetylation of the gene-associated histones.
- The expression patterns of cyclin D1, cyclin E, p21/waf1 and p27/kip1 in inflammatory bowel disease (IBD) may indicate their contribution in epithelial cell turnover and their possible implication in IBD-related dysplasia-carcinoma.
- The expression of p21 protein depends on p53 protein largely in normal gastric mucosa and dysplasia, but not in gastric carcinoma.
- role of pathway in regulating G1-S transition and apoptosis along with RFT
- Results suggest that p150(Sal2), acting in part as a p53-independent regulator of p21 and BAX, can function in some cell types as a regulator of cell growth and survival.
- p21(Waf1) can activate the transcription of p16(INK4); this effect is GC-box dependent; and the transcription factor Sp1 plays a key role in this event
- hepatitis B virus X protein natural variants have differential effects on p21 expression
- activation of the p53-p21WAF1 pathway and overexpression of cyclin D1 are induced during tumor cell differentiation by beta-catenin
- Low p21 protein levels are caused by reduced p21 gene transcription and sensitize cisplatin-treated TGCT cells to the Fas death pathway
- p21 or p21B do not have a role in causing resistance to doxorubicin or mitomycin/5-fluorouracil in breast cancer
- p21/waf1 could potentially function as an assembly factor in HTLV-1 infected cells.
- Data suggest that dihydrotestosterone reverses titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and increased association of p21 with Cdk2 complexes mediates the androgen-induced growth inhibition of breast cancer cells.
- p21Cip1/WAF1 and HER2/neu togehter have a role in progression of breast neoplasms
- in normal cells, p21 exerts a dual role in mediating DNA damage-induced cell cycle arrest and exit before mitosis
- Data show that ERK1/2-mediated phosphorylation of hepatitis B viral X-gene (HBx) regulates HBx function and localization, and that HBx repressed transcription from the p21(WAF1/Cip1) promoter.
- hRAD9 and p53 co-regulate p21 to direct cell cycle progression by similar molecular mechanisms.
- P21 expression stimulates promoters of six p21-responsive human genes and the cytomegalovirus promoter, as well as an artificial promoter containing NFkappaB response elements.
- Disruption of p53-p21/WAF1 cell cycle pathways contributes to tumor progression and worse clinical outcome of hepataocellular hepatoma.
- Relation between expression, DNA ploidy and human papillomavirus infection in cervical carcinoma.
- Data show that extracellular signal-regulated kinase 3 (ERK3) is conjugated to ubiquitin via its free NH(2) terminus, and that N-terminal tags stabilize expression of p21 but not that of substrates ubiquitinated on internal lysine residues.
- p53 and/or p21(WAF1/CIP1) genotype may influence the progression during gastric tumorigenesis.
- p21WAF1 gene expression is regulated by histone deacetylase inhibitors at the post-transcriptional level in HepG2 cells
- Stat3 mediates expression of p21waf1.
- Cyclin D1, p53, and p21Waf1/Cip1 have roles in progression of serous epithelial ovarian cancer
- physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21.
- Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116.
- pdcd4 represses the transcription of the mitosis-promoting factor cyclin-dependent kinase (CDK)1/cdc2 via upregulation of p21(Waf1/Cip1)
- Monocytic differentiation of the promyelomonocytic cell lines U937 and HL60 is associated with the upregulation of Brap2 expression concomitantly with the upregulation and cytoplasmic relocalization of p21.
- P21Cip1 positively regulates the cytotoxic action of thymidylate synthase inhibitors, negatively regulates the cytotoxic action of IFN-gamma, and enhances S-phase exit after thymineless stress in colorectal carcinoma cells.
- Cystathionine gamma-lyase has a role in regulating cell proliferation via a H2S-dependent modulation of ERK1/2 phosphorylation and p21Cip/WAK-1
- Tax1 markedly activated transcription from the cdk inhibitor p21(cip1/waf1) promoter in comparison to Tax2, suggesting that upregulation of p21(cip1/waf1) may account for the differential inhibition of cellular replication kinetics
- repression of hTERT by endogenous p53 is mediated by p21 and E2F
- PGA2 stabilizes the p21 mRNA through an ERK-independent increase in cytoplasmic HuR levels and an ERK-dependent association of HuR with the p21 mRNA
- absence of p21 produced no overt alteration of the lifespan of the INK4a/ARF-null mice
- We conclude that overexpression of PKCdelta in human colon cancer cells induces multiple antineoplastic effects that depend on the activities of p21(Waf1/Cip1) and p53.
- p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli
- survivin can reduce the cell growth inhibition and apoptosis, and p53 elevates the p21 level, which may attenuate the cell death in the quercetin-treated human lung carcinoma cells
- c-myc downregulation and release from the endogenous p21WAF1/CIP1 promoter contributes to transcriptional activation of the p21WAF1/CIP1 in HeLa cells
- p21CIP1 mRNA is absent in human T-LBL biopsies and T-ALL cell lines at a high frequency. However, unlike p15INK4B, reduced p21CIP1 expression in T-LBL/ALL is independent of dense promoter-associated CpG methylation
- Nuclear clusterin function is proapoptotic in colon cancer when induced by APC or chemotherapy in the context of p21 expression.
- A significant increase in p21, p53, and fas mRNA expression were reported in the proximal incompetent veins; negative correlation between media apoptotic index and p21 mRNA expression was found.
- IRF-1-p300 interface as an allosteric modifier of DNA-dependent acetylation of p53 at the p21 promoter
- P21waf1/cip1 system alteration may be an early and frequent event in tongue carcinogenesis.
- c-Myc antagonized the induction of p21Cip1 mediated by oncogenic H-, K-, and N-Ras and by constitutively activated Raf and ERK2
- Deletion mutants of p21 promoter reveal that sequences between -270 and -264, forming a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. E2A-dependent expression of endogenous p21 gene was also inhibited by Snail.
- in tumor cells lacking functional p53 and/or p21, p14(ARF) impaired mitotic entry and enforced a primarily cytoplasmic localization of p34(cdc2) that was associated with a decrease in p34(cdc2) kinase activity and reduced p34(cdc2) protein expression
- The cytoplasmic localization of p21,Cip1 may be the molecular mechanism whereby breast cancer cells circumvent TNF-alpha-induced growth inhibition and apoptosis.
- We conclude that (1) clinically achievable doses of ionizing radiation can trigger CDKN1A-dependent accelerated senescence in some human tumor cell lines that express wild-type TP53.
- p21WAF expression is induced by 5-Aza-CdR by demethylation of p73 leading to p53-independent apoptosis in myeloid leukemia
- differentiation-inducing agents, particularly sodium butyrate, suppress growth of oral squamous carcinoma cells through apoptosis and induce cell differentiation possibly through mechanisms involving COX-2, p27Kip1 and/or p21WAF1/Cip1 in vitro and in viv
- Rb, p21Cip1, and PCNA have roles in cAMP-mediated inhibition of DNA replication and S phase progression
- Results demonstrate the importance of posttranslational stabilization of p21 protein by WISp39 in regulating cellular p21 activity.
- p21Cip/WAF1 induction is a determinant in the regulation of colonic proliferation by the ERK pathway.
- increased expression leads to increase in apoptosis independent of p53
- the mutually antagonistic action of two RNA-binding proteins, Hu and hnRNP K, control the timing of the switch from proliferation to neuronal differentiation through the post-transcriptional regulation of p21 mRNA
- p21 is a common target of all TGF-beta superfamily pathways
- Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ(2), but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation.
- results suggest that p21 and FasL gene activation is required for myeloid leukemia cell survival or maturation but not for cell death via Sp1 and NFkappaB as regulators of these genes
- low molecular weight forms of cyclin E may contribute to tumorigenesis through their resistance to the inhibitory activities of p21 and p27 while sequestering these CKIs from the full-length cyclin E
- Results showed a significant, progressive loss of expression of p21(Cip1/WAF1) with advancing papillary thyroid carcinomas.
- Mitf-mediated activation of p21Cip1 expression and consequent hypophosphorylation of Rb1 will contribute to cell cycle exit and activation of the differentiation programme
- Quercetin and ellagic acid combined increase the activation of p53 and p21(cip1/waf1.
- Expression of CDKN1A and Gadd45 proteins acting on cell cycle checkpoints and DNA repair in PCa relative to the presence of oxidative DNA damage was measured.
- pioglitazone generally does not modulate p21 transcription in human cancer cell lines
- P21 and Bax have roles in progression of cutaneous malignant melanoma
- p21WAF1/CIP1 behaves as a transcriptional coactivator in a gene-specific manner implicated in cell differentiation.
- Temporal ectopic expression of p21(Cip1) arrested cell proliferation, inhibited Cdk2 and Cdk4 activities, suppressed retinoblastoma phosphorylation and arrested cells in both G1 and G2 cell cycle phases.
- Lack of functional p21 resulted in the accumulation of cells in G2/M phase of the cell cycle and markedly enhanced p14 ARF-induced apoptosis.
- Dehydroepiandrosterone increased the expression of p53 and p21 mRNAs.
- galectin-8 is a modulator of cellular growth through up-regulation of p21
- Glioblastoma cells show different and independent responses in their p53 and p21 pathways to ionizing radiation
- In the abscence of this this gene in colorectal carcinoma cells, toxicity of histone deacetylase inhibitors was reduced.
- demonstrated that epigallocatechin-3-gallate activates growth arrest and apoptosis primarily via tumor suppressor p53-dependent pathway that involves the function of both p21 protein and Bax protein
- These data implicate p21 as a pivotal macrophage facilitator of HIV-1 life cycle; regulators of p21, such as CDDO, may provide an interventional approach to modulate HIV-1 replication.
- unable to arrest tumor progression in oral squamous cell carcinoma
- Hyperphosphorylated p21 activates the Cdc2 kinase in the G2/M transition.
- This study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG (primary open-angle glaucoma) in the Caucasian population.
- expression was found to be associated with poorer prognosis and tumor aggressivity in oral squamous cell carcinoma
- TP53, CDKN1A, CDKN2A, and CDKN2B have roles in tumorigenesis in skin melanomas, but none of them is a main mutation target for melanoma tumorigenesis
- the mechanism of p21 protection is by direct inhibition of cdk2 activity and that cisplatin-induced apoptosis in kidney failure is caused by a cdk2-dependent pathway
- expression of p53, MDM2, and p21Waf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis
- Significant increase in squamous cell carcinoma of the head and neck in the presence of two p21 polymorphisms may be a marker of genetic susceptibility.
- physiological concentrations of conjugated linoleic acid inhibit growth of colon cancer cells with either wild-type or mutant p53
- In cholesteatoma, co-expression of p21 and pERK1/2 was prominent, whereas in retro-auricular skin there was hardly any co-expression.
- mitochondrial stress causes resistance to apoptosis through a p21-dependent pathway
- The Cyclin-Dependent Kinase Inhibitor p21 plays key roles in cell cycle regulation, and was methylation-negative in myeloid neoplasia.
- p21cip1/waf1 has a role in growth, apoptosis and differentiation in human colon carcinoma cells
- This study using lymphocyte proliferation as a model evaluates the effects of recombinant p21 protein on lymphocyte proliferation, cytokine expression, and the mechanism of antiproliferative effects of p21 in activated lymphocytes.
- Cdk2 destabilizes p21 via the cy2 cyclin-binding motif and p21 phosphorylation
- p300 regulates p63-dependent transcription of p21
- There is enhanced G2/M arrest by NF-kappa B-dependent p21waf1/cip1 induction.
- p21 is one specific target of PR3; PR3-mediated p21 cleavage prevents monocytic differentiation
- Results suggested that the overexpression of p21(WAF1/CIP1) in conjunction with the loss of p53 expression was a stronger predictor of survival benefit than either molecule alone in Japanese serous-type advanced ovarian cancer.
- p73 upregulates p21 transcript abundance (TA) in BC tissues and upregulated p21 TA may result from E2F1 upregulation of p73 but not from E2F1 directly
- p53 and p21 act in series in mediating cell cycle arrest. However, the two risk factors, p53 proline homozygosity and p21 arginine allele, although part of a common causal pathway, appear to act in a mutually exclusive manner.
- Induction of p21WAF1 expression increases tumor cell survival and may result in recurrences at treated sites after cryotherapy.
- P21(WAF1/Cip1) plays a major role in angiogenesis in breast cancer, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium.
- Sp3 D-domain modulates its protein levels and activation of the p21(CIP1/WAF1) promoter
- p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1
- PPARdelta partially rescued prostate epithelial cells from growth inhibition and also dramatically inhibited sulindac sulfide-mediated p21WAF1/CIP1 upregulation.
- increased mRNA stability is the major mechanism of p21(WAF/CIP1/SDI1) elevation in the hydroxyurea-induced growth arrest of human fibroblasts
- Overexpression of p21 correlates with chromosomal instability and serves as an adverse prognostic predictor for patients with esophageal squamous cell carcinoma.
- Tumor suppressor activity of RUNX3 is associated with its ability to induce p21 (WAF1/Cip10) expression.
- a change of intracellular distribution of p21CIP1 from nucleus to cytoplasm along with differentiation appears to be anti-apoptotic
- p21WAF1/CIP1 may have a role in oral tongue squamous cell carcinoma progression
- ERK activation and p21 and N-cadherin upregulation are required for genistein-induced neuronal differentiation
- KSHV vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells; it is shown that this arrest is mediated by p21 in a p53-independent manner.
- p21(CDKN1A) levels after low doses of UV-irradiation may be controlled in a p53-dependent manner without severe reduction.
- These data suggest a physiological role of SREBP-1a in p21 regulation.
- musashi homolog 1 ability to regulate progenitor maintenance is through the translational inhibition of the cyclin-dependent kinase inhibitor p21WAF-1.
- In summary, the p53/p21 pathway is mainly responsible for GC-induced apoptosis, but the coordinated activation of the p53/p21 and p16 pathway is responsible for GC-induced endothelial cell senescence through a Rb-dependent mechanism.
- In addition, the transcription factor Sp1 that is involved in the Ras/ERK-mediated control of p21WAF1 regulation in VSMC in response to PDGF has now been identified.
- Tax1 induced transcriptional upregula inhibitors p21(cip1/waf1) (p21) and p27(kip1) (p27), and marked suppression of hematopoiesis in immature CD34 cells.
- Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21(WAF1/CIP1) and p27(Kip1) levels under the growth inhibitory conditions.
- Data demonstrate that ubiquitination of p21(Cip1/WAF1) requires a functional interaction between p21(Cip1/WAF1) and the cyclin E-Cdk2 complex.
- p21WAF1/CIP1 expression in metastatic prostate cancer cell lines is enhanced as a result of demethylation of the DNA
- Checkpoint kinase 1 plays a primary role in the protection of cells from death induced by replication fork stress, whereas p21 mediates through its role in regulating entry into S phase
- Results describe the opposite effect of ERK1/2 and JNK on p53-independent p21WAF1/CIP1 activation involved in the arsenic trioxide-induced human epidermoid carcinoma A431 cellular cytotoxicity.
- Gfi1 associates with G9a and HDAC1 on the promoter of the cell cycle regulator p21Cip/WAF1, resulting in an increase in K9 dimethylation at histone H3
- hSNF5 binds the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes.
- The signaling pathway for colonocyte apoptosis following toxin A exposure involves p38-dependent activation of p53 and subsequent induction of p21(WAF1/CIP1), resulting in cytochrome c release and caspase-3 activation through Bak induction.
- Our results indicate that the TP53 P allele is associated with a worse prognosis (P=0.011) while P21 polymorphism genotypes did not reveal any statistically significant result (P>0.05).
- MDM2 has critical roles in the regulation of p21 and E2F1 expression, stability and function [review]
- p21/WAF1 inactivation may confer a strong resistance to paclitaxel in noncancerous breast epithelial cells harboring a p21/WAF1 mutant.
- The p21(waf1/cip1) gene is a primary 1alpha,25(OH)2D3-responding gene with at least three VDR binding promoter regions, in two of which also p53 co-localizes.
- p50 might target or anchor p21 to pol delta complex upon certain DNA damage such as adriamycin treatment.
- This study demonstrates for the 1st time the involvement of MAPK-cyclin D1-p21(cip)machinery during cell growth inhibition and apoptosis of human vascular smooth muscle cells induced by cysthationine gamma-lyase overexpression.
- p21(Waf1/Cip1) promoter methylation may be a critical biological barrier to postpone the aging process
- The role of histone deacetylases in the expression of CDKN1A in normal and neoplastic human colon cells is reported.
- These results indicate that early recruitment of p21 protein to DNA-damage sites is a NER-related process dependent on interaction with PCNA, thus suggesting a direct involvement of p21 in DNA repair.
- LKB1 has the potential to induce p21 expression in collaboration with LMO4, GATA-6, and Ldb1 through the p53-independent mechanism
- Subcellular targeting of ING1 by phosphorylation-dependent 14-3-3 binding regulates P21 expression.
- low doses of Taxol for 18 h determined the upregulation of p53 and p21 waf expression concomitantly with a decrease of the anti-apoptotic Bcl-2.
- In mammalian cells, translesion DNA synthesis (TLS) is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency.
- These data demonstrate a critical role for FAK in the regulation of cyclin-dependent kinase inhibitors (CDKIs) through two independent mechanisms: Skp2 dependent and Skp2 independent.
- Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells
- results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21(CIP1/WAF1) activation in SNU-16 cells
- p21-mediated cytoprotection against hyperoxia involves regulation of Bcl-XL and is uncoupled from its ability to inhibit proliferation
- BRCA1 could act as a CTD kinase inhibitor and, as such, contribute to the regulation of p21 gene expression
- suggest a novel retinoic acid (RA)-signaling, by which RA-induced p21 induction and complex formation with cyclin E/cyclin-dependent kinase 2 (CDK2) diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis
- Loss of a functional mitochondrial electron transport chain inhibits cell-cycle progression, and we postulate that this occurs through the decreased concentration of reactive oxygen species, leading to downregulation of p21CIP1/WAF1.
- analysis of novel mechanisms for apoptosis induction by silibinin involving p53-caspase 2 activation and caspase-mediated cleavage of Cip1/p21
- UV induces p21 degradation through an Skp2 and ubiquitin-independent pathway
- In particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome.
- Possible involvement of CDKN1A and CDKN1B variants in the etiology of breast cancer.
- P21(waf1/cip1) is identified as a target gene of DDX3, and the up-regulation of p21(waf1/cip1) expression accounted for the colony-suppressing activity of DDX3.
- EGFR-mediated induction of enterocyte proliferation requires MAPK-dependent increase in p21(waf1/cip1) expression in intestinal epithelial cells.
- Expression of AR protein in PC3-Lenti-AR cells resulted in transactivation of p21 and growth inhibition in culture and in mouse xenografts. Such inhibition was due to induced G1 arrest as documented by expression changes in p27 and p45(SKP2) proteins.
- expression of either AP-2gamma or AP-2alpha induces p21 and inhibits breast carcinoma cell growth
- p53 preferentially occupied the promoters of growth arrest genes p21 and GADD45 in senescent normal human diploid fibroblasts.
- HDACi induction of the cyclin-dependent kinase inhibitor p21(waf1) has been shown to require ataxia-telangiectasia mutated (ATM).
- p21WAF1/CIP1 and 14-3-3 sigma expression was several fold higher in degenerated aortic valves with no calcification versus degenerated aortic valves with calcification on both transcription and translation levels
- These data show that specific interaction of the Akt2 isoform with p21 is key to its negative effect on normal cell cycle progression.
- Klotho normally regulates cellular senescence by repressing the p53/p21 pathway
- This novel finding indicated that IKKbeta could mediate cytoplasmic p21 accumulation via activation of its downstream target Akt, which was known to phosphorylate p21 and lead to cytoplasmic localization of p21.
- RNPC1a is required to maintain the stability of p21 transcript induced by p53.
- The degradation of p21(WAF1/CIP1) induced by PP2Cgamma was mediated in a proteasome-dependent manner.
- We find an over-abundance of p21 due to reduced protein turnover, possibly due to the loss of activity of the CSA/CSB E3 ubiquitylation pathway
- Risk of cancer is markedly increased in heavy smokers (>20 pack-years) with squamous-cell carcinoma carrying an amino acid substitution.
- association between locally advanced breast cancer and one particular polymorphism of the p21 gene
- p27 is widely expressed in gastric well differentiated endocrine tumors (GWDETs), while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes.
- GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences
- Dox-induced decrease in KAP1 sumoylation is essential for Dox to induce p21 expression and subsequent cell growth inhibition in MCF-7 cells
- p21 gene promoter in combination with a rAAV vector is potentially usable for the development of a low-dose radiation-inducible vector for cancer gene therapy.
- APMCF1 participates at least partially in cell cycle regulation through regulating genes such as p21 and TIMP3.
- Chromatin immunoprecipitation analyses show that LKB1 is recruited directly to the p21/WAF1 promoter, as well as to other p53 activated promoters, in a p53-dependent fashion.
- association of Zac1 with importin alpha1 is also involved in regulating the transactivation activity of Zac1 on the p21WAF1/CIP1 gene and protein expression
- Identification of a functional target site for the transcription factor, nuclear factor I (NFI), in the basal promoter from the p21 gene.
- While the DNA replication checkpoint is unlikely to regulate the assembly of a p21 promoter initiation complex, it signals to one or more factors involved in the process of transcriptional elongation.
- The crucial role of p21Cip/WAF1 in the extracellular signal-regulated kinase pathway-dependent antiproliferative responses by tautomycetin was confirmed by using p21Cip/WAF1 gene-deleted HCT-116 cells.
- Vpr may regulate HIV-1 gene expression via interacts with the N- and the C-terminal domains of p21.
- p53 and Ki-67 were expressed with increasing frequency, and bcl-2, p21, and mdm-2 with decreasing frequency in thyroid carcinoma progression. p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression.
- p21 and p27 in carcinoma of oral cavity have roles in progression of squamous cell carcinomas
- individual variations in radiosensitivity and in the level of induction of TP53 (and consequently CDKN1A) are congruent, irrespective of the genetic background of the nontransformed fibroblasts
- Has important role in mediating the apoptotic effect of histone deacetylase inhibitors.
- This is the first demonstration of GSK-3beta as the missing link between UV-induced ATR activation and p21 degradation.
- Loss of p21(WAF1) facilitates AML1-ETO-induced leukemogenesis.
- PI 3-K signaling pathway suppresses phorbol 12-myristate 13-acetate-induced expression of p21WAF1/Cip1 in human leukemia cells, and that this effect is partly mediated by PKC zeta.
- p21(WAF1/CIP1) (p21), a negative regulator of the cell division cycle, exhibits proteasome-sensitive turnover and ubiquitination in a tumor cell line.
- p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy
- Multiple lines of evidence indicate that the transcriptional process of p21 is downregulated by depressed zinc status in HepG2 cells.
- CDA1 induces p53- and MEK/ERK1/2 MAPK-dependent expression of p21 by acting through the p53 responsive element in the p21 promoter and this contributes to its antiproliferative activity
- Binding of p21(Cip1) to apoptosis signal-regulating kinase 1 (ASK1) requires ASK1 kinase function and may involve phosphorylation of S98
- The expression of p21 in the patients with wild-type EGFR tended to be associated with poor overall survival.
- c-Abl and p53 can be recruited to the region containing p53 binding site of p21 promoter, and c-Abl increases the DNA binding activity of p53 to the p21 promoter
- results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest
- study demonstrates that PKCdelta-mediated phosphorylation of 146Ser residue of p21WAF1/CIP1 is a novel mechanism for enhancing the cellular stability of the inhibitor protein by blocking caspase-3-mediated degradation
- the RUNX2 and YAP65 interaction has a novel role in oncogenic transformation that may be mediated by modulation of p21(CIP1) protein expression
- findings do not suggest mutations or polymorphisms of p21B to play a major role with respect to either breast cancer risk or sensitivity towards chemotherapy
- p21 is upregulated after radical prostatectomy for prostatic neoplasms.
- CARF may exert a vital control on p53-HDM2-p21(WAF1) pathway that is central to the cell cycle control, senescence, and DNA damage response of human cells
- stress-induced premature senescence (SIPS) from hydrogen peroxide is associated with a transient increase in DNA-binding activity of p53 and an increased expression of p21(WAF-1) in human hTERT fibroblasts
- The down-expression of p21(WAF1) mRNA in colorectal carcinoma might be associated with histone hypoacetylation in chromatin but not with biological behaviors.
- reactive oxygen species induce p21(Cip1) degradation through an NES-, Skp2-, and ubiquitin-dependent pathway
- livers maintained effective removal of cells from the cell cycle by overexpression of p21
- adhesion of mantle cell lymphoma and other non-Hodgkin lymphoma cells to bone marrow stromal cells resulted in a reversible G(1) arrest associated with elevated p27(Kip1) and p21 (WAF1) proteins
- induction of p21 protects against sulforaphane-induced mitotic arrest in LNCaP cells
- immunoreactivity of p53, MDM2, WAF1, and BCL-2 were measured in soft tissue sarcomas cases consisting of 54 low-grade, 40 intermediate-grade, and 58 high-grade sarcomas
- fibrillar collagen can also arrest cells at the G2 phase, which is mediated in part by p21(CIP1)
- a new role for YY1 as both an inducer of p53 instability in smooth muscle cells, and an indirect repressor of p21WAF1/Cip1 transcription, p21WAF1/Cip1-cdk4-cyclin D1 assembly and intimal thickening.
- ataxia telangiectasia mutated protein phosphorylation of ZBP-89 contributes to HDACi induction of p21(waf1) gene expression
- p21 acts as a negative regulator of p53 stability in different cell types and may provide a negative regulatory loop that limits p53 induction.
- Ski siRNA increased TGF-beta-induced Smad2 phosphorylation and p21 expression.
- The association of p53 codon 72 and CDKN1A codon 31 polymorphisms with oral cancer risk in a Taiwanese population were investigated.
- TSG101 negatively regulates p21 levels, and up-regulation of TSG101 is associated with poor prognosis in ovarian cancer
- Low expression of p21 was detected but had no effect on survival or recurrence in the univariate analysis.
- PKC epsilon exerts its oncogenic activity through deregulation of the cell cycle via a p21/Cip1-dependent mechanism
- Overexpression of p21/WAF1 is an independent prognostic factor in hepatocellular carcinoma which favors survival.
- Data show that functional cooperation between TrkA and p75(NTR) accelerates neuronal differentiation by increased transcription of GAP-43 and p21(CIP/WAF) genes via ERK1/2 and AP-1 activities.
- Rhabdomyosarcoma cells overexpressing MDM2 abrogated ceramide-mediated p21(Cip1/Waf1) induction, G(2) arrest and the late ensuing apoptosis.
- Treatment with vorinostat and sorafenib synergistically induces apoptosis in chronic myelogenous leukemia cells through a process that involves Mcl1 down-regulation and inhibition of p21(CIP1) induction.
- Histone deacetylase inhibitors enhance lexatumumab-induced apoptosis via a p21Cip1-dependent decrease in survivin levels
- Elevated expression of cell-cycle regulators p16(INK4A), p21(CIP1), and cytoplasmic/nuclear beta-catenin correlated with increased colorectal cancers risk, as did elevated expression of survivin and human telomerase reverse transcriptase.
- p21WAF1/CIP1 is a common transcriptional target of retinoid receptors RAR and RXR
- Downregulation of caveolin-1 expression affects bleomycin-induced cell cycle arrest and subsequent cellular senescence that is driven by p53 and p21.
- Upon DNA damage, histone H2A.Z is first evicted from the p21 promoter, followed by the recruitment of the Tip60 histone acetyltransferase to activate p21 transcription.
- type I IFN prolongs cell cycle progression by p21WAF1/CIP1 induction in human colon cancer cells
- Treatment with Magnolia plant extracts upregulated epression of this protein in a bladder cancer cell ilne.
- Data indicate that overexpression of the transcriptional cofactor FHL2 contributes to breast cancer development by mediating transcriptional activation of MAPK target genes known to be involved in cancer progression, such as p21.
- ectopically BRCA2-expressing cells have different intracellular levels of Aurora A, Aurora B, p21, E2F-1, and pRb, suggesting a BRCA2-mediated suppression of polyploidy via stabilization of the checkpoint proteins levels
- The apoptogenic activity of BM-ANF1 was mediated through p53 tumor-suppressor gene expression followed by the expression of p21(Cip1) and p27(Kip1)linking it with cell cycle arrest at G1 phase in cancer cells.
- Study reports that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).
- Data show that knockdown of p21Cip1, but not p16(INK4a) or Rb, allows cells to bypass premature senescence that is induced by BS69 knockdown.
- 15-48 aa region of p21 is essential for basal expression by preventing degradation by the proteasome
- p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle.
- TLX recruits histone deacetylases to repress transcription of p21(CIP1/WAF1) and pten and regulate neural stem cell proliferation
- Results found that the activation of p21 is primarily by HNF4alpha1 interacting with promoter-bound Sp1 at both the proximal promoter region and at newly identified sites in a distal region (-2.4 kb)and does not need direct DNA binding by HNF4alpha1.
- Nuclear accumulation of p21 accompanied by accelerated senescence may be an integral component of the response of human fibroblasts to UVC-induced DNA damage, irrespective of their DNA repair capabilities.
- Our results point to an antiproliferative function of the unliganded ER alpha through its physical interactions with p21(WAF1) that may also explain the favorable prognosis of ER alpha-positive breast cancers.
- Both PD98095 and dicoumarol were capable of blocking TNFalpha production but had only a small effect on p21Waf1 expression
- cell cycle inhibitor p21Waf1/Cip1 genes were found significantly upregulated in the cases with progressive sarcoidosis
- that Rac1 is an essential player for mediating the induction of cyclin D1 and p21(Cip1) by HRG in breast cancer cells
- There were no apparent differences in immunostaining for p21 in myomas or in normal myometrium
- The combination of p53 and p21 expressions in biopsy findings can thus predict the histological effectiveness of hyperthermochemoradiotherapy.
- ERK activation with some other pathway(s), activated through the HGF receptor, are required to up-regulate p16 and p21 expression, that of p21 contributes to suppression of Cdk2 activity leading to inhibition of proliferation of HGF-treated HepG2 cells.
- p21 has an important role in the cellular response to normal replicative stress and its absence leads to a "chronic DNA damage" state that primes the cell for p53-dependent apoptosis.
- the ability of Tbx2 to repress the p21 gene is enhanced in response to a stress-induced senescence pathway, which leads to a better understanding of the regulation of the anti-senescence function of Tbx2.
- levels of p53/p21waf1 mRNA in blood lymphocytes collected before chemotherapy may predict the chemoresponses of lung cancer patients.
- Results suggest that a combined analysis of three P21 polymorphisms might better predict the risk of lung cancer than the analysis of a single polymorphism.
- TP53 Arg72Pro polymorphism, but not p73 G4C14>A4TA4 and p21 Ser31Arg, contribute to risk of cutaneous melanoma
- The culture of cells in the Cl(-)-replaced medium significantly increased expressions of p21 mRNA and protein without any effects on p53.
- Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21(WAF1/CIP1) induction.
- These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases.
- linear relationship and prognostic role of the p53/p21/PCNA pathway in gastrointestinal stromal tumors. Abnormalities of the p53/p21WAF1 pathway lead to increased proliferating states, thereby triggering the progression of GISTs.
- The expression of p21(WAF1/Cip1) and p27(Kip1) was increased at both protein and mRNA levels by hydroxytyrosol, a main phenol of olive oil.
- discrete PKCs trigger distinctive responses when activated in different phases of the cell cycle via a common mechanism that involves p21 Cip1 up-regulation.
- loss of p21's cyclin-dependent kinase inhibitory property results in hyperphosphorylation of estrogen receptor-alpha, with subsequent increased gene expression of estrogen receptor-regulated genes
- These results imply that HIF-1alpha functions as an up-stream player in the p21-mediated growth arrest of keratinocytes.
- p21Cip1 is prominent within the dentate gyrus and restricted to the subgranular zone of the developing transgenic p21-deficient mouse dentate gyrus, where it might act to restrain neurogenesis.
- We immunohistochemically analyzed the expression of p21, p27, p14, p16, p53 and proliferation marker Ki67, in 67 low and high grade astrocytic tumors.
- the -KTS-containing variants of WT1 are directly involved in the regulation of p21(Waf1/Cip1) expression and the subsequent suppression of lymph node metastasis in human lung squamous cell carcinoma
- Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of Small-cell neuroendocrine carcinoma of the uterine cervix.
- p21 is a direct target of miR-106b. Its silencing plays a key role in miR-106b-induced cell-cycle phenotypes.
- PUMA exerts a negative feedback on p53 and p21, leading to p21-dependent growth suppressive and survival changes.
- Our results indicate that nicotinamide treatment attenuates p21WAF1 expression through Sp1 downregulation, and suggest a possible involvement of nicotinamide metabolism in cellular gene expression.
- We propose that BARD1 reduces BRCA1 transcriptional activity, and that this at least partly involves BRCA1/BARD1 E3 ubiquitin ligase activity, which is disrupted by the C61G mutation.
- present study did not demonstrate a significant association between P21 / WAF1 genotype and oral squamous cell carcinoma
- intracellular accumulation of P21WAF1 may be one of the mechanisms which contribute to cigarette smoke extract-induced inhibition of cell proliferation
- Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest.
- CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells.
- the p21G251A polymorphism significantly correlates to the subgroup of locally advanced breast cancers (p = 0.0049)
- ERK and JNK MAPK/Elk-1/Egr-1 signal cascade is required for p53-independent transcriptional activation of p21(Waf1/Cip1) in response to curcumin in U-87MG human glioblastoma cells
- p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 are expressed in human corneal endothelial cells despite donor ages.
- BAF180 suppresses tumorigenesis, at least in part, through its ability to regulate p21.
- variations in c-myc and p21(WAF1) expression delay apoptosis making PBL resistant to sodium butyrate for several hours
- High zinc status in normal bronchial epithelial cells upregulates p53 expression which in turn elevates p21, inducing G2/M blockage.
- Report overexpression of cyclin D1, D3, and p21 in renal carcinomas with Xp11.2 TFE3-gene fusion.
- CDKN1A expression increased with increasing grade in meningiomas.
- results support Killin as a missing link between p53 activation and S phase checkpoint control designed to eliminate replicating precancerous cells, should they escape G(1) blockade mediated by p21.
- S100/A11 and p21 gene expression was also found to be significantly lower in acute and chronic atopic dermatitis skin.
- Mutations of K-ras and overexpression of the ras p21 were detected in 11% and 76% of the colorectaltumors, respectively
- disruption of the spindle-assembly checkpoint does not directly influence p53 activation, but the shortening of the mitotic arrest allows cyclin E-CDK2 to be activated before the accumulation of p21(CIP1/WAF1).
- Genistein induces the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins in prostate cancer cells.
- increased expression of p21(Waf1/Cip1) and several other p53-regulated genes is caused by diminished Pdcd4 expression
- p21, acting as a sensor of cellular stress, may have potent and wide roles in lung responses triggered by cigarette smoke. [REVIEW]
- Zbtb4 associates with the Sin3/histone deacetylase co-repressor and represses expression of P21CIP1 as part of a heterodimeric complex with Miz1.
- oxidative stress-induced expression in biliary epithelial cells in primary biliary cirrhosis is associated with activation of the ATM pathway
- Cdc6 determines utilization of p21(WAF1/CIP1)-dependent damage checkpoint in S phase cells
- S100A11 targets Rad54B to sites of DNA DSB repair sites and has a role in p21-based regulation of cell cycle
- Genetically programmed cell death is related the p21 and p27 pathways in pseudophakic bullous keratopathy.
- crucial role exerted by p21Cip1/WAF1 in PPARgamma action in thyroid neoplasm
- Our study has identified p21 protein expression as important biological marker which may indicate the progression of laryngeal squamous cell carcinoma.
- The combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in microsatellite instability-high colorectal cancer.
- The procyanidin-mediated induction of apoptosis and cell-cycle arrest in esophageal adenocarcinoma cells is not dependent on p21(Cip1/WAF1).
- p21 could be a potential mediator of survivin suppression at the transcriptional level
- Simultaneous knock-down of both p21 and p27 significantly enhanced doubling time, clonogenicity and cell cycle progression in a prostate cancer cell line.
- Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp1.
- Andrographolide inhibits human colorectal cancer Lovo cell growth by G1-S phase arrest and inducing the expression of p53, p21 and p16.
- HDAC4 is a novel regulator of colon cell proliferation through repression of p21
- Zac1 might be involved in regulating the p21(WAF1/Cip1) gene and protein expression through its protein-protein interaction with p53 and HDAC1 in HeLa cells.
- Deletion of NLS motifs resulted in failure of ING1b to completely localize to the nucleus and inhibited its ability to induce p21WAF1 expression.
- p21 might play an important role in chemosensitivity to anticancer agents
- CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation
- experiments showed that p21 deficiency in stromal fibroblasts accelerates breast tumor growth through cell non-autonomous mechanism(s); propose that p21 regulation is intimately linked with the ability of stromal cells to affect tumor growth
- The p53-dependent transcriptional regulation of p21 in response to DNA damage by ultraviolet radiation and ionizing radiation compared.
- These results shed light on the molecular mechanism of action of GHRH antagonists in tumor tissues and suggest that the antineoplastic activity of GHRH antagonists could be considered for the treatment of cancers expressing p21.
- the analysis of p21cip1, p27kip1, and p16INk4a by immunohistochemistry could be useful in the management of patients with papillary thyroid carcinoma
- p21 is a negative regulator of PCNA-pol eta interaction.
- Increased expression of p21/WAF/Cip1 in primary leukemic blasts suggests that elevated p21/WAF/Cip1 levels may contribute to specific features observed in AML1-positive leukemia.
- positive expression rate and co-expression rate of P21WAF1/CIP1 and P16 proteins could reflect the malignant grade of glioma to some extent, and they can be considered as a sensitive index for glioma grading
- PCNA promotes the ubiquitylation and degradation of the CDK inhibitor p21 in cells irradiated with low dose of ultraviolet radiation
- defines the degradation of p21 as a critical aspect of replication licensing in human cells
- p21(WAF1/CIP1) is an important factor in the sensitivity of cells to the growth inhibiting and apoptotic effects of OSU03012.
- Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF
- AP4 directly repressed p21 by occupying four CAGCTG motifs in the p21 promoter via its basic region.
- Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21(CIP1) expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels.
- p21 mRNA expression in vinyl chloride exposed workers was significantly higher than in nonexposed workers.
- knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway.
- Results indicate that both p16(INK4a) and p21(WAF1/CIP1) are required for the opioid growth factor (OGF)-OGF receptor axis to inhibit cell proliferation in normal cells.
- CDKN1A/p21 appears to be an essential target of miR-17-92 during B-cell lymphomagenesis, which suggests the miR-17-92 polycistron has distinct targets in different B-cell lymphoma subtypes.
- TsA markedly down-regulated the expression of cyclin D1 and CDK4, up-regulated the expression of p21WAF1 and p53 and induced cell cycle arrest at the G1 phase in MCF10A-ras cells
- Absence of p21 expression is associated with biologically less aggressive phenotypes in gallbladder and extrahepatic bile duct cancer.
- Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest.
- a mechanistic link between JNK activity and liver cell proliferation via p21 and c-Myc and suggest JNK1 targeting can be considered as a new therapeutic approach for HCC treatment.
- These results showed that the expression of cyclin D1, p21 and p27, alone or in combination, are early events in gastric tumorigenesis and may serve as a candidate molecular marker for the early gastric carcinoma.
- These results highlight the role of p21 in counteracting inappropriate proliferation stimuli for genome stability maintenance.
- The p21 codon 31*C- and DRD2 codon 313*T-related genotypes/alleles, but not XRCC1 codon 399, hOGG1 codon 326, and DRD1-48 polymorphisms, are correlated with the presence of leiomyoma.
- RASSF1A can mediate cell cycle arrest and senescence in human cancer cells by p53-independent regulation of p21(Cip1/Waf1).
- MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription
