|
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 SMAD4(NM_005359.5) Search again
Product ID:
HQP102069
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
DPC4, JIP, MADH4, MYHRS
Gene Description:
SMAD family member 4
Target Gene Accession:
NM_005359.5(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
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.
Validated result:
|
|
| A | B |
|
Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
|
Gene References into function
- structure of DNA-binding domain
- DNA-binding protein
- Alterations in tumor-suppressor gene DPC4 may play an important role during the tumorigenesis of pancreatic cancer.
- A point mutation in Smad4 abolished binding to SMIF.
- smad4 may play an important role in the regulation of TGFbeta inducible gene expression and subsequent growth inhibition.
- Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot.
- TLV-1 tax represses Smad-mediated TGF-beta signaling.
- Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.
- In this study, the expression of Smad4 protein appeared to be correlated with the depth of invasion of esophageal SCC
- interactions between AR, Smad3, and Smad4 may result in the differential regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression
- Restoration of transforming growth factor Beta signaling by functional expression of smad4 induces anoikis.
- determined the crystal structure of a complex between a conserved Smad4 binding fragment of Ski and the MH2 domain of Smad4 at 2.85 A resolution
- Smad4/DPC4 has a role in TGF-beta-mediated inhibition of cell proliferation in vitro and in vivo
- Phenotypic and functional changes associated with TGF-beta1-induced fibroblast terminal differentiation are differentially regulated by Smad2, Smad3, and Smad4.
- the re-expression of the Smad4 gene by either method partially restored TGF-beta responsiveness in FaDu cells with respect to both growth inhibition and expression of p21WAF1/CIP1 and p15INK4B
- Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer.
- Interaction domains of Smad4 and ERalpha are mapped and shown to be essential for transcriptional repression of ERalpha by Smad4.
- Smad4 is not required for nuclear translocation of Smad2 and Smad3, but is needed for activation of at least certain transcriptional responses.
- Results suggest that the transcriptional cross talk between the TGFbeta-regulated Smads 3 and 4 and hepatocyte nuclear factor-4 is mediated by specific functional domains in the two types of transcription factors.
- Human HCC transfectants express a mutant Smad2(3S-A). Serine residues of SSXS motif were changed to alanine. They have impaired Smad2 signaling. Forced expression of Smad2(3S-A induced TGFB secretion & resistance to TGFB-induced growth inhibition.
- results suggest carcinogenesis in the biliary tract epithelium in anomalous pancreaticobiliary ductal union (APBDU) is accompanied by multistep mutational events; inactivation of DPC-4 gene accumulates late in progression of biliary tract adenocarcinoma
- Smad4 is sumoylated and has a role in the regulation of TGF-beta signaling through Smads
- Smad-4 had no effect on the basal activity of the MCP-1 promoter, but showed the ability to decrease both Smad-3 and Tat-induced transcription of the MCP promoter in human astrocytic cells
- oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation
- duration of TGF-beta-Smad signaling is a critical determinant of the specificity of the TGF-beta response.
- SUMO-1 modification serves to protect Smad4 from ubiquitin-dependent degradation and consequently enhances the growth inhibitory and transcriptional responses of Smad4.
- A G/A transition at 31 bp upstream-nontranslated regions of exon 8 of Smad 4 was found in cervical cancer cells, highlighting an important role for Smad 4 in human cervical tumors.
- Smad4 interaction with CAN/Nup214, and nuclear import requires structural elements present only in the full-length Smad4; Smad3 and Smad4 have different susceptibility to inhibition of import by cytoplasmic retention factor SARA
- Smad4 was expressed in all thyroid cell lines and controls analyzed, differently from other classes of tumors where Smad4 expression was deleted.
- Sumoylation of Smad4 mainly occurs at lysine 159 and facilitates Smad-dependent transcriptional activation; PIAS-mediated sumoylation of Smad4 is regulated by the p38 MAP kinase pathway
- DACH1 bound to endogenous NCoR and Smad4 in cultured cells; Smad4 was required for DACH1 repression of TGF-beta induction of Smad signaling
- Smad2, Smad3 and Smad4 contribute to the regulation of TGF-beta responses to varying extents, and exhibit distinct roles in different cell types
- endometrium, stromal cellS and epithelial cells express Smad3, -4, and -7 mRNA and protein
- Inactivation of DPC4 gene late in neoplastic progression of pancreatic carcinoma. Variation of DPC4 gene activation in biliary tract carcinoma. Common bile duct carcinoma and pancreatic carcinoma have similar molecular alternations.
- SMAD3 and SMAD4 activate gadd45beta through its third intron to facilitate G2 progression following TGFbeta treatment
- DPC4/Smad4 inactivation by mutation or deletion appears to be very rare in pancreatic endocrine tumors.
- Mutations in SMAD4 abrogate its function in transducing the signaling of TGF-beta, which plays an important role in various stages of cancer formation.
- DPC4 mutations in appendiceal adenocarcinomas suggests involvement of DPC4 and nearby genes on chromosome 18q (DCC and/or JV-18) in the pathogenesis of appendiceal adenocarcinomas
- DPC4 is involved in the development of pancreatic carcinoma and is a late event in pancreatic carcinogenesis.
- DLX1 is expressed in hematopoietic cells in a lineage-dependent manner and that DLX1 interacts with Smad4 through its homeodomain
- CHIP can interact with the Smad1/Smad4 proteins and block BMP signal transduction through the ubiquitin-mediated degradation of Smad proteins.
- Two missense mutations in the C-terminal domain of Smad4, D351H (Asp351-->His) & D537Y (Asp537-->Tyr), from colorectal cancer cells cannot interact with either TGF-beta-induced phosphorylated Smad2 or Smad3.
- SMAD4 has a role in regulation of large-scale chromatin unfolding
- Smad4 protein stability is regulated by ubiquitin ligase SCF beta-TrCP1
- Homozygous deletion, followed by inactivating nonsense or frameshift mutations, is the predominant form of MADH4 inactivation in pancreatic cancers.
- Smad4 showed most significant prognostic differences in stage I gastric cancer patients.
- decreased nuclear Smad4 expression associated with progression to prostate cancer; loss of BMP2 and Smad4 related to progression to a more aggressive phenotype
- Inactivation of the DPC4 gene contributes to the genesis of colorectal carcinoma through allelic loss
- Thirty-eight colon carcinomas were analyzed by immunohistochemistry for cell adhesion molecules (E-cadherin, beta-catenin, CD44), cell cycle regulatory proteins (cyclin D1, p27, p21), mismatch repair proteins (hMLH1, hMSH2), cyclooxygenase-2 and DPC4
- exon 2 (belonging to the MH1 domain) and exons 8, 10, 11 (belonging to the MH2 domain) are not altered in renal cell carcinoma
- a significant role of impaired SMAD4 function in the pathogenesis of small intestinal adenocarcinomas
- The most transcriptionally active splice variants of Smad4 are made in macrophages (but not SMCs) of fibrofatty lesions and are upregulated after cell differentiation from monocytes. Cyclin inhibitors are induced by Smads. Fibrous plaque SMCs make Smad4.
- Dpc4 may have a role in invasiveness of intraductal carcinoma
- Our findings suggest that BAMBI transcription is regulated by TGF-beta signaling through direct binding of SMAD3 and SMAD4 to the BAMBI promoter.
- Regulated cytoplasmic and nuclear retention may play a role in determining the distribution of Smads between the cytoplasm and the nucleus in both uninduced cells and upon TGF-beta induction.
- DPC4 mutations were found in 40% of pancreatic adenocarcinoma cell lines and 58% of primary tumors. They were mostly deletions in exons 8-11, and 1 frameshift in exon 9.
- Squamous cell cervical cancer showed loss of Smad4 protein expression or reduced expression.
- gene expression regulation by TGF beta under Smad4 knockdown
- Daxx suppresses Smad4-mediated transcriptional activity by direct interaction with the sumoylated Smad4 and has a role in regulating transforming growth factor beta signaling
- expression of Smad4 was significantly lower in diffuse-type gastric adenocarcinoma than intestinal-type gastric adenocarcinomas
- TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and targets Smad4 into the nucleus; mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta
- The level of expression of SMAD4 was found to be a more sensitive marker than 18q21 allelic imbalance and SMAD4 mutations, which were of no prognostic significance for colorectal cancer patients.
- Smad4 is targeted for degradation by multiple ubiquitin ligases that can simultaneously act on R-Smads and signaling receptors
- DPC4 inactivation was found in 75% of patients examined for lethal metastatic pancreatic neoplasms.
- Cancer cell lines harboring Smad4 point mutations exhibited rapid Smad4 protein degradation due to the effect of SCF(beta-TrCP1).
- Results suggest that loss of Smad4 expression may be involved in HPV16-induced carcinogenesis of head and neck squamous cell carcinomas.
- Tsc-22 binds to and modulate the transcriptional activity of Smad3 and Smad4
- demonstrate that Smad4 induces apoptosis by regulating Bim splicing as an initial intrinsic signal in ERalpha-positive cells
- Smad4 is both frequently mutated and deregulated by aberrant splicing in thyroid tumours and these alterations may contribute as an early event to thyroid tumorigenesis.
- SMAD4 gene alteration was found in patients, diagnosed with multiploid colorectal carcinomas.
- There are two populations of TGF-beta target genes that are distinguished by their dependency on Smad4.
- Smad4, but not Smad2, mediates TGF-beta1-induced MMP-2 expression in invasive extravillous trophoblasts
- Functional evidence was provided for a switch of the Smad4 pathway, from tumor-suppressor to prometastatic, in the development of breast cancer bone metastasis.
- deletion constructs of the promoter and mutational deletion of specific transcription factor binding sites indicated that Smad3/4 and AP-1 binding sites mediated the TGF-beta1 response on LTBP-3
- Smad4 plays the role in the transcriptional activation of NF-kappaB.
- A nonsense mutation of the SMAD4 gene in exon 5 codon 245 CAG (glut) -->TAG (stop) was found in neck squamous cell carcinoma cell line CAL27.
- Hereditary haemorrhagic telangiectasia and juvenile polyposis in patients with SMAD4 mutations.
- Biallelic inactivation of SMAD4 through homozygous deletion in breast cancer cell lines and invasive ductal carcinomas.(
- One mechanism for positive regulation of TLR2 induction involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction
- These data define the expression control of an essential BM component as a novel function for the tumor suppressor Smad4.
- shRNA interference suppresses endogenous Smad4 gene expression and subsequently modulates cell growth and apoptosis.
- aberration of the Transforming Growth factor-beta pathway, as indicated by a reduction or absence of Smad4 expression, promotes carcinogenesis of oral squamous cell carcinoma
- identified a total of 47 protein species with a Smad4-dependent expression
- mRNA expressed in human granulosa-luteal cells at oocyte retrieval.
- Cooperates with lymphoid enhancer-binding factor 1 to activate c-myc expression.
- DPC4 regulates MMP9 and may inhibit the proliferation of colon cancer cell by restraining growth and inducing apoptosis
- Loss of SMAD4 expression was significantly more frequent in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum
- SMAD4 loss in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation
- Smad4 mediates down-regulation of E-cadherin induced by TGF-beta in PANC-1 cells, at least in part, through Snail and Slug induction.
- Transgenic Smad4 has a role in the maintenance of hematopoietic stem cell self-renewal and reconstituting capacity.
- Our results indicate that absence of Smad4 expression correlated significantly with liver metastases regardless of the time of their occurrence and represents a promising new biomarker to predict liver metastasis in colorectal cancer patients.
- Mutations of K-ras and Dpc4 genes can accumulate already in non-malignant, inflammatory pancreatic tissue, suggesting its applicability in monitoring of further destruction of pancreatic tissue and progression into malignancy.
- Correlation of the expression of S100A8 and S100A9 revealed that the microenvironments of tumours which lacked expression of Smad4, had significantly reduced numbers of S100A8-immunoreactive (p = 0.023) but not S100A9-immunoreactive (p = 0.21) cells.
- examined the possible deterioration in the pathway in human squamous cancer cell lines, focusing on intracellular localization of S100C/A11 and its functional partners Smad3 and Smad4
- Proinvasive activity of BMP7 through SMAD4/src-independent and ERK/Rac/JNK-dependent signaling pathways in colon cancer cells is reported.
- Results show that Arkadia specifically activates transcription via Smad3/Smad4 binding sites by inducing degradation of the transcriptional repressor SnoN.
- These results suggest an important role for cross talk among Smad, p38 MAPK, JNK, and PI3K pathways in mediating the augmented expression of hAT(1)R following TGF-beta1 treatment in human fetal pulmonary fibroblasts.
- Smad4 siRNA treatment completely abolished TGFb-induced early gene upregulation, indicating the absence of the rapid activation of Smad signaling.
- combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy.
- study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine-needle aspirate samples
- 5 nonsense, 6 frameshift and 4 missense mutations (2 new) were associated with juvenile polyposis syndrome.
- Mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus.
- functional characterization of a tumorigenic mutation in Smad4(E330A); findings show this mutant & a Smad3 mutant (Smad3 E239A) failed to activate transcription in response to TGFbeta stimulation because of defects in oligomerization
- Smad4 has a role in extracellular matrix composition in cervical cancer
- Large genomic deletions of SMAD4, BMPR1A and PTEN are a common cause of JPS.
- We failed to find evidence of genomic deletions or amplifications affecting the Smad4 locus on chromosome 18 in advanced prostate cancer.
- loss of Smad4 contributes to aberrant RON expression and cross-talk of Smad4-independent TGF-beta signaling and the RON pathway promotes an invasive phenotype
- vidence for a cross talk between Smad4 and the Wnt/beta-catenin pathway in pancreatic carcinoma cells.
- Data show that the expression of key transcription factors, phosphorylated Smad1 protein, and the nuclear accumulation of Smad1 and Smad4 are inhibited by Ubc9 silencing.
- Smad4 is a target molecule for functional inactivation in cervical cancer.
- In MSI CRC this is associated predominantly with impaired BMPR2 expression and in MSS CRC with impaired SMAD4 expression.
- DPC$ might be involved in preventing the tumor metastasis by inhibiting tumor angiogenesis.
- TGF-beta-induced and basal state spontaneous nuclear import of Smad4 require importin 7 and 8.
- loss of Smad4, leading to aberrant activation of STAT3, contributes to the switch of TGFbeta from a tumor-suppressive to a tumor-promoting pathway in pancreatic cancer
- Data demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is recruited to TGFbeta response elements.
- Deleted in pancreatic carcinoma locus 4 might be an important biomarker for malignant transformation and be involved in inducing apoptosis by modulating Bcl-2/Bax balance.
- Smad4 mediates transcriptional regulation through three mechanisms: Smad4 binding to a functional SBE site in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites via interaction with AP1 family, and Smad4 impact on transcription of AP1 factors
- The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS was 45% in the largest series of patients to date
- TGF-beta1-induced cell growth inhibition by up-regulating p16 expression and cellular apoptosis by activating caspase 3 was Smad4-dependent
- The inactivation of SMAD4 is similar in familial pancreatic adenocarcinomas as in sporadic pancreatic adenocarcinomas.