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Validated All-in-One™ qPCR Primer for CFTR(NM_000492.3) Search again
Product ID:
HQP000948
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ABC35, ABCC7, CF, CFTR/MRP, MRP7, TNR-CFTR, dJ760C5.1
Gene Description:
CF transmembrane conductance regulator
Target Gene Accession:
NM_000492.3(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:
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| A | B |
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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. |
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Summary
This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily that is involved in multi-drug resistance. The encoded protein functions as a chloride channel and controls the regulation of other transport pathways. Mutations in this gene are associated with the autosomal recessive disorders cystic fibrosis and congenital bilateral aplasia of the vas deferens. Alternatively spliced transcript variants have been described, many of which result from mutations in this gene. [provided by RefSeq].
Gene References into function
- CFTR gene transcription is regulated by a DNase I hypersensitive site
- mutational analysis of the entire coding region in idiopathic pancreatitis
- TG(m)T(n) polymorphism has an effect on splicing in transgenic mice
- 'Chronic complications' reveal mainly the effect of a long-term absence of previously recognized CFTR functions. In contrast, the 'unique presentations' provide new insight into the role of CFTR in different tissues. Review.
- disulfide bond structure
- mutations and phylogeny (place of origin)
- wild type CFTR elevates the acid-gated Na(+) current of ASIC1a/2a in part by altering the kinetics of extracellular Na(+) interaction.
- non-conventional trafficking through the early secretory pathway
- Cl(-) channel and a regulator of other transport proteins and the large number of disease-causing CFTR mutations is the reason for a variable genotype-phenotype correlation and sometimes unpredictable clinical manifestation
- CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis.
- role for functional CFTR in regulation of lysozyme secretion in human airways.
- actin must be directly associated with CFTR to elicit its activation, further suggesting that this channel protein may bind actin as well.
- CFTR is an apically resident ion channel whose activity is regulated by the activation of the cAMP mediated second messenger cascade.
- Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases
- Localisation of wild-type and DeltaF508-CFTR in nasal epithelial cells.
- mapping of DNase I hypersensitive sites (DHS) within the locus
- Cysteine residues in the nucleotide binding domains regulate the conductance state of CFTR channels
- Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis
- CFTR/Actin binding
- Discrimination between CF cells and CFTR-corrected epithelial cells by a membrane potential-sensitive probe and digital imaging technique that detects response to cAMP in the majority of CFTR-corrected cells, but only in a small proportion of CF cells.
- data support a model where nucleotide-binding domains form dimers with the ATP-binding sites at the domain-domain interface
- A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification
- Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor.
- calcium channel inhibitors induce surface expression in cystic fibrosis cultured epithelial cells of mutated protein
- Men with the CFTR mutation, the 5T allele only, and those without CFTR mutation have few differences in genital phenotype. Low testicular volume is observed in men without the CFTR mutation and those with the 5T allele only.
- Glutathione levels and BAX activation during apoptosis due to oxidative stress in cells expressing wild-type and mutant protein
- Csp has a role in regulated CFTR trafficking at the plasma membrane. [CYSTEINE STRING PROTEIN]
- Sequence alignment of representative vertebrate CFTR with the aim of generating hypotheses on the functional significance of conserved and variable residues.
- The allele and genotype frequencies of the tetranucleotide tandem repeat (TTR) of CFTR intron 6B were analyzed in eight ethnic populations of the Volga-Ural region, including Bashkir, Tatar, Chuvash, Mari, Mordvinian, Udmurt, Komi-Permyak, and Russian
- Role of Hsp40 co-chaperone Hdj-1 in CFTR turnover with HSP70
- Introduction of the most common mutations into human P-glycoprotein disrupts packing of the transmembrane segments.
- A novel natural product compound enhances cAMP-regulated chloride conductance of cells expressing CFTR[delta]F508
- These studies demonstrate that luc-containing YAC vectors can be used to study CFTR expression in human cells, and that regulatory elements responsible for decreased CFTR expression in response to PMA are not located in the 5'-flanking sequence.
- substitution of two residues eliminates aggregation of a 111-amino acid peptide derived from the C-terminal portion of the cystic fibrosis transmembrane conductance regulator (CFTR).
- mutations in CFTR nucleotide binding domain region rescue the CFTRDeltaF508 defect
- The comparison of primary sclerosing cholangitis patients with healthy controls showed no significant difference in the frequency of CFTR mutations
- CFTR gene mutation is observed with trypsinogen levels more than 60 ng/mL.
- CFTR may contribute to blastocoele formation in the early human embryo
- Analysis by mass spectrometry of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens. Compound heterozygosity.
- CFTR channels are regulated by a t-SNARE complex that may tune CFTR activity to rates of membrane traffic in epithelial cells.
- Aberrant interactions between the mutant first nucleotide binding domain (NBF-1) of CFTR and phospholipid chaperones contribute to the trafficking defect identified for the DeltaF508 cystic fibrosis mutant.
- Aminoglycoside antibiotics suppress a premature stop mutation in a Cftr -/- mouse carrying a human CFTR-G542X transgene.
- Pancreatitis risk showed complex inheritance and was highest in individuals with abnormalities in both pancreatic ducts(CFTR) and acini (PST1)
- most CFTR-positive ADPKD cysts also express NKCC1 suggests that transepithelial Cl(-) secretion in ADPKD involves molecular mechanisms similar to secretory epithelia.
- It is concluded that I148T occurs on at least three haplotypes and the complex allele I148T + 9T + 3199del6 is associated with a classic CF phenotype
- Our findings suggest that CFTR may modulate neurosecretory activity of PNEC/NEB possessing O(2) sensor function
- interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3-cotransport isoform 3
- These results provide a molecular basis for calcium-induced bicarbonate secretion in pancreatic duct cells and highlight the importance of CFTR in epithelial bicarbonate secretion induced by various stimuli.
- Normal CFTR protein function can be associated with homozygous (Delta)F508 mutation. cAMP-dependent Cl(-) conductance seen in homozygotes could be due to residual CFTR activity & may explain the mild phenotypes seen in some (Delta)F508 homozygotes.
- 13 CF patients originating from the south west region of France and bearing 1811+1.6kbA>G (11 compound heterozygotes and two homozygotes) were studied.
- Regulation of channel gating by AMP-activated protein kinase modulates cystic fibrosis transmembrane conductance regulator activity in lung submucosal cells.
- The interaction between syntaxin 1A and this chloride channel is different from syntaxin 1A-SNARE interactions.
- An ATP-hydrolysable conformation of NBD2 is essential for the regulation of the VSOR by the CFTR protein. VSOR is first channel regulated by CFTR through its NBD2.
- results show that the ClC-3B PDZ-binding isoform resides in the Golgi where it co-localizes with a small amount of CFTR
- disease manifestation in CF is modulated by loci in the partially imprinted region 3' of CFTR that determine stature, food intake and energy homeostasis, such as the Silver-Russel-Syndrome candidate gene region and LEP.
- RNA probe derived from exons 10-13 stained cystic fibrosis transport regulator mRNA in both the epidermis and the sweat gland to a similar extent
- CFTR modulates gene expression in airway epithelial cells while located in a macromolecular signaling complex at the plasma membrane
- Overexpression of mutant AMPK-alpha1 enhanced forskolin-stimulated I short-circuit currents, consistent with dominant-negative reduction in inhibition of CFTR by endogenous AMPK.
- The NBF1 and R domains of CFTR catalyze a Co2+/Mn2+/Mg2+-ATPase activity inhibited by Cd2+ and orthovanadate.
- mutation generates a novel internalization sequence and enhances endocytic rates
- Not only are CFTR and ENaC activated together in duct salt absorption, but ENaC activation depends on functioning CFTR.
- Bashkortostan was shown to differ in CFTR mutation spectrum from other regions of Russia
- Alternative 5' exons of the CFTR gene show developmental regulation
- the role of CFTR protein in the pathogenesis of congenital abscense of vas deferens suggests that this phenotype can represent a mild form of cystic fibrosis.
- Multiple anions can bind simultaneously within CFTR channel pore, and repulsive interactions between bound anions speeds anion exit from pore.
- Lyotropic anions bind tightly to outer mouth of CFTR pore, involving interaction with fixed positive charge and coordination of multiple permeant anions within pore. Anion binding in pore may be important in normal anion permeation mechanism.
- A genetic marker within CFTR, a gene adjacent to FOXP2, has a strong association with common language impairment.
- effect on cystic fibrosis transmembrane regulator exon 9 splicing of natural and site-directed sequence mutations
- Our results support a model in which specific TM6 residues make important contributions to a single, localized anion selectivity filter in the CFTR pore, and contribute to multiple anion binding sites both within and on either side of the filter region
- CFTR mutations in cytsic fibrosis patient families needs genetic counseling to prevent the disease risk in subsequent pregnacies.
- conserved CFTR sequences between species are examined for potential regulatory elements. Regions of introns 2, 3, 10, 17a, 18, and 21 and 3' flanking sequence corresponding to human CFTR DNase I hypersensitive sites showed high homology in cow and pig.
- Increased prevalence of CFTR abnormalities in PSC (primary sclerosing cholangitis) as demonstrated by molecular and functional analyses which may contribute to the development of PSC in a subset of patients with inflammatory bowel disease.
- Impact on physicians of variation in test-report content for CF was assessed.
- CFTR selectivity control by glutamate and ATP in epithelial cells
- Equilibrative nucleoside transporters (hENT1, hENT2) together with adenosine kinase and 5'-nucleotidase play a crucial role in the regulation of CFTR through an adenosine-dependent pathway in human airway epithelia.
- A single nucleotide change at codon 158 in exon 4 of the CFTR gene ABCC7 was detected in an asymptomatic individual who carried deltaF508 and had a family history of cystic fibrosis (CF).
- Results suggest that carriers experience minimal adverse psychological effects, although a negative social stigma may be attached to carrying the CF gene mutation.
- A frameshift mutation in CFTR is not rare.
- Two novel mutations were found in a Taiwanese male CF patient.
- Expression of dominant negative Rme-1, an epsin homology domain containing protein, in cystic fibrosis transmembrane conductance regulator (CFTR)-expressing cells results in the expansion of recycling compartments. [Rme-1 protein]
- CFTR channel gating is regulated through phosphorylation of NHERF PDZ2 domain by protein kinase C
- A new missense mutation X1481W in the CFTR gene causes translation of an elongated protein of 1484 AA & is associated with a milder cystic fibrosis phenotype.
- A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases was perfomed.
- The type IVB pili of Salmonella enterica serovar Typhi bind to the cystic fibrosis transmembrane conductance regulator.
- Mutations in the CFTR gene represent the major cause of idiopathic chronic pancreatitis in Brazilian patients.
- At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly in high altitude pulmonary edema-susceptible subjects
- CAL retains CFTR in the cell and
- presence of some active F508del-CFTR in the apical cell membrane implys that factors other than the CFTR-mediated residual Cl- secretion determine the age of onset of Pseudomonas colonization.
- the C-terminal PDZ binding motif of CFTR has a role in its diffusional mobility at the plasma membrane
- CFTR dysfunction is associated with altered Src signaling, resulting in the persistence of gap junction connectivity in primary and transformed CF airway cells.
- Determination of TG repeat number will allow for more accurate prediction of benign versus pathogenic 5T alleles in cystic fibrosis.
- Lipid raft localization of CFTR is required for signaling in response to Pseudomonas aeruginosa infection, signaling that is needed for the coordination of innate immunity to Pseudomonas aeruginosa lung infection.
- Polymorphisms in CFTR are associated with an increased risk of developing pancreatitis but are not a risk for developing pancreatic neoplasms.
- CFTR has adenylate kinase activity that regulates gating. When functioning as an adenylate kinase, CFTR showed positive cooperativity for ATP suggesting its two nucleotide binding domains may dimerize.
- Insufficient maturation and transport of DeltaF508 CFTR from endoplasmic reticulum to apical membrane to support CFTR-mediated chloride secretion in cystic fibrosis colon.
- a genomic sequence containing exon 9 of CFTR is part of a large duplicated sequence unit, provisionally named LCR7-20; many genomic regions containing LCR7-20's either have been misassembled or are missing in current versions of the human genome sequence
- cftr gene expression is down-regulated in Alzheimer's disease
- cystic fibrosis transmembrane conductance regulator exon 9 alternative splicing is regulated by an intronic polypyrimidine-rich element downstream of the donor site
- The role of CFTR in submucosal gland fluid secretion was tested in human airways. The reduced rate of gland fluid secretion after CFTR inhibition shown here provides strong evidence for the involvement of CFTR in glandular epithelial fluid transport.
- Gross gene rearrangements in the CFTR gene. Discussion of mutational mechanisms that may be associated with cystic fibrosis.
- four novel CFTR mutations, i.e., IVS2 + 28 (intron 2), 459T > A (exon 4), EX17a_EX18del (exons 17-18), and IVS22 + IG > A (intron 22), in black cystic fibrosis patients
- syntaxin 8 contributes to the regulation of CFTR trafficking and chloride channel activity by the SNARE machinery
- DRA activates CFTR by increasing its overall open probablity. Activation of CFTR by DRA was facilitated by their PDZ ligands and binding of the SLC26T STAS domain to the CFTR R domain.
- analysis of assembly of CFTR in the plasma membrane
- epithelial cells endogenously expressing CFTR efficiently process this protein to post-Golgi compartments
- Although cystic fibrosis is relatively rare in Turkey, CFTR mutations are responsible for the majority of congenital bilateral absence of vas deferens in Turkish males.
- external epitope-tagged constructs used to elucidate the itinerary and kinetics of wild type and DeltaF508 CFTR in the endocytic pathway and visualize movement of CFTR from the surface to intracellular compartments
- CFTR mutations are risk factors for chronic pancreatitis.
- role of CFTR in adherence, uptake and IL-8 production by respiratory epithelial cells in a model of infection of polarized respiratory epithelial cells with P. aeruginosa
- G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype.
- role of the lectin Htm1p in the degradation process of CFTR
- HspBP1 interferes with the CHIP-induced degradation of immature forms of the cystic fibrosis transmembrane conductance regulator (CFTR) and stimulates CFTR maturation.
- CFTR purification and crystallization
- endocytosis in facilitated by myosin VI and dab2 by a mechanism that requires actin filaments
- Exposure to TGFbeta causes dramatic changes in the expression and localization of the apical membrane chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR
- the DeltaF508 mutation alters interactions between the transmembrane domains critical for function.
- evidence that heterodimerization of the NBD1 and NBD2 nucleotide binding domains of CFTR is required to generate optimal catalytic activity
- results indicate that alterations in external Cl(o)(-) alone and not the Cl(-)/HCO(3)(-) ratio regulate the gating of CFTR
- human cystic fibrosis transmembrane conductance regulator degradation in yeast involves Hsp40 and Hsp90 molecular chaperones and Ydj1p/Hlj1p
- a single allelic CFTR mutation is sufficient to augment IL-8 secretion in response to LPS. This is not a result of increased LPS receptor expression but, rather, is associated with alterations in MAPK signaling.
- TGF-beta 1 significantly downregulated CFTR mRNA and cAMP-dependent current in nasal polyp cultures; data suggests that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression
- CFTR has a transcription-dependent spatial arrangement.
- CFTR genes from 46 African Americans and 356 Hispanic Americans were screened. 8 new mutations (1 missense mutation, 1 splice-site mutation & 6 frame-shift mutations) & 21 distinct rare mutations not in the commercial mutation panels were identified.
- The requirement for both CFTR and vesicular transport pathways in retinal pigment epithelium suggests vesicular insertion of CFTR may underlie the release of ATP.
- A mutation is identified in about 80% of the CFTR genes derived from congenital bilateral absence of the vas deferens patients. (review)
- Loss of CFTR and CFTR-driven autocrine ATP signaling may underlie defective cell volume regulation and dysregulated ion, water, and acid-base transport in cystic fibrosis airway epithelia.
- CFTR mRNA and protein were localized in human endometrial epithelial cells and the amounts varied in a cyclic manner
- splicing modulation restores the cystic fibrosis transmembrane conductance regulator function
- ceramide originating from basolateral sphingomyelin acts on activated CFTR from the cytosolic side, hindering anion secretion
- the di-acidic exit code plays a key role in linking CFTR to the COPII coat machinery
- structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation
- Semen hyperviscosity could be considered a "minimal clinical expression" of cystic fibrosis; CFTR gene sequence variations may constitute the genetic basis for this disease.
- CFTR heterogeneity in the Iranian population suggesting the need to concentrate on sequence analysis to find isolated mutation in patient with cystic fibrosis.
- The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane
- CFTR is regulated through a MAP kinase signaling cascade dependently or not on an activation of adrenergic beta-3 receptor.
- We conclude that neither nonconserved segment is an essential element of PKA- or nucleotide-dependent CFTR regulation.
- Inhibition of CFTRDeltaF508 ubiquitination can increase its cell surface expression and may provide an approach to treat cystic fibrosis
- hydrophobic side chain interactions of Phe508 are required for vectorial folding of NBD2 and the domain-domain assembly of CFTR
- the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR
- both nucleotide-binding domains (NBDs)contribute to channel gating, NBD1 binds ATP but supports little hydrolysis, and ATP binding and hydrolysis at NBD2 are key for normal gating.
- transfected in hamster kidney cells, structurally diverse open channel blockers of CFTR appear to share a common molecular mechanism of action that involves interaction with a positively charged amino acid side chain.
- Mutations in CFTR is associated with cystic fibrosis
- Role for CFTR gene polymorphism in the progression of alcohol-related pancreatic disease. Alcoholics with homozygous (TG)11 alleles in intron 8 of the CFTR gene appear to be protected against decreased bicarbonate concentration in pancreatic juice.
- results show that the absence of functional CFTR protein causes neither an abnormality in mucin O-glycosylation nor an increase in mucin sulphation
- Data indicate that the adenylate kinase reaction at nucleotide-binding domain 2 of the cystic fibrosis transmembrane conductance regulator contributes to the inhibitory effect of ADP.
- Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete CFTR reconstitution.
- Genotype-phenotype correlations showed a wide heterogeneity in CTFR gene in the french population.
- This 18-month pilot project showed an unexpected low incidence of CF (1/8885) in South of France, with only six CF children detected among 43,489 neonates
- Hydrosalpinx epithelium undergoes epithelial transformation with elevated CFTR expression, which may lead to increased transepithelial electrolyte and fluid secretion.
- metabolic fate of deltaF508 CFTR and associated ERM proteins in the cystic fibrosis lung
- ATP-driven tight dimerization of CFTR's cytoplasmic nucleotide-binding domains is linked to opening of the ion channel, suggesting that CFTR employs a molecular mechanism similar to that used by other ABC transporters.
- results directly link ATP-driven tight dimerization of CFTR's cytoplasmic nucleotide-binding domains to opening of the ion channel in the transmembrane domains
- 3849+10kbC->T and 2789+5G->A alleles are splice site mutations associated with a milder course of cystic fibrosis disease.
- We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough.
- pivotal foles of CFTR and PSTI during pancreatic exocrine secretion
- The Asian CF phenotype is as severe as the white controls with the homozygous delta F508 phenotype but is worse in some outcomes, especially in Asian females.
- CFTR compound heterozygosity CFTRdele2,3 and R117H and wild type alleles of the poly-T-tract in intron 8 are reported in a patient with pancreatitis.
- CFTR protein misprocessing leads to mild cystic fibrosis phenotype
- The frequency of cystic fibrosis mutations has been reported to be higher in patients with chronic rhinosinusitis than in unaffected controls.
- the mutation spectrum of CFTR in congenitl bilateral absence of vas deferens patients does not overlap with the Caucasian CFTR mutation spectrum.
- Data show that the major degradation pathway of the cystic fibrosis transmembrane conductance regulator with F508 deletion from the endoplasmic reticulum is independent of calnexin.
- Functional interaction between CFTR and PR65, a regulatory subunit of the protein phosphatase 2A (PP2A), was shown.
- CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown in resting culture conditions
- Cytokine-induced posttranscriptional regulation of CFTR gene expression and the modulation of CFTR mRNA stability linked to its 3' untranslated sequence in HT-29 and Calu-3 cells are reported.
- sAC signaling pathway is involved in the regulation of CFTR function in human airway epithelium and thereby provides a link between the level of intracellular HCO(3)(-)/CO(2) and the modulation of HCO(3)(-)-conductive CFTR function by cAMP/PKA.
- respiratory epithelial cell line bearing DeltaF508 mutation on CFTR released more PGE2 than control cell line
- First direct evidence for phosphorylation-dependent binding of the the CFTR regulatory (R) domain and its role in CFTR activation.
- annexin A1 downregulation in cystic fibrosis knock-out mice and patients
- CFTR mutations appear not to be involved in female infertility.
- Results describe several small-molecule correctors of defective DeltaF508-cystic fibrosis transmembrane conductance regulator cellular processing.
- CFTR analysis in infertile men & fertile population as control excludes involvement of CFTR gene variants in sperm production
- A cluster of aromatic amino acids, which includes F508 and straddles the two nucleotide binding domains (NBDs), might be directly involved in the interaction of the CFTR NBD1/NBD2 heterodimer with the channel-forming membrane-spanning domains.
- A difference in relative frequencies and spectrum of CFTR mutations in Indian cystic fibrosis cases.
- CFTR is expressed in cultured alveolar epithelial type IIcells and may contribute to cAMP-regulated apical-basolateral ion and fluid transport
- suppression of CFTR expression may represent an adaptive response of mucosal epithelium to an exogenous oxidant stress
- The TG12 repeats in the cystic fibrosis transmembrane conductance regulator (CFTR) gene tended to have a weak association with chronic pancreatitis
- release of the cystic fibrosis transmembrane conductance regulator from early endoplasmic reticulum biosynthetic machinery requires an energy-dependent maturation step
- Serum response factor may be involved in the regulation of CFTR gene expression.
- In chronic P.aeruginosa lung infection, the transcription of four NF-kappaB-regulated cytokine genes is maximal in the presence of WT CFTR: the interleukin-8 (IL-8), IL-6, CXCL1, and intracellular adhesion molecule 1 (ICAM-1) genes.
- in the cystic fibrosis cell lines, CFBE41o- and CFT1-C2, targeted NHERF1 overexpression induced the redistribution of CFTR from the cytoplasm to the plasma membrane and rescues CFTR activity
- results indicate that deltaF508 CFTR, when rescued in CFBE41o- human airway epithelial cells, is poorly responsive to signalling pathways known to regulate wild-type CFTR
- the ATP-induced Cl- channel could be an alternative Cl- channel to CFTR in middle ear epithelial cells
- A cell-free filtrate of P. aeruginosa reduced CFTR-mediated transepithelial Cl(-) secretion by inhibiting the endocytic recycling of CFTR and thus the number of WT-CFTR and mutant channels in the apical membrane in polarized human airway epithelial cells
- CFTR is regulated by a direct interaction with the protein phosphatase 2A
- Thus, these results demonstrate that UTP and PMA activation of CFTR occurs independently of increases in intracellular cAMP and extend the findings of earlier studies of CFTR regulation by PKC in Xenopus oocytes to a mammalian anion secreting epithelium.
- Projection structures of CFTR from two-dimensional crystals analysed by electron crystallography displayed two alternative conformational states.
- ATP drives tight dimerization of CFTR's cytoplasmic nucleotide binding sites.
- Patients with two identified CFTR mutations which include the R117H/7T anomaly should be followed up routinely as they remain susceptible to severe lung disease.
- CFTR gene mutations are common but not the only reason for the occurrence of congenital bilateral absence of the vas deferens -dependent male infertility
- Although there are more than 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of them are uncommon and only limited information exists regarding genotype-pulmonary phenotype relationships.
- Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
- The prevalence of CF was estimated by using the proportion of F508del homozygous cases out of all CF patients, as reported in various studies (19-44%) from Indian subcontinent.
- CFTR associated mutants G551D and G1349D have different sensitivity to CFTR potentiators
- Nucleotide-binding domains of cystic fibrosis transmembrane conductance regulator catalyze adenylate kinase activity but not ATP hydrolysis.
- The results provide a converging mechanism to link regulation of CFTR and airway cell inflammation through adenosine and adenosine receptors.
- in our cohort of infertile males, the frequency of CFTR heterozygosity is twofold higher than in the general population
- The study suggests that Rab4 regulates the channel through multiple mechanisms that include protein-protein interaction, GTP/GDP exchange, and channel protein trafficking.
- CP, grade III CP, pseudocysts, and pancreatic strictures were more common among patients who were CF gene positive.
- A carrier of the F508del mutation of the CFTR gene was detected in the Malay population.
- substituting a cysteine at 338 of CFTR can create an adventitious metal binding site
- A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 of the 120 chromosomes.
- DeltaF508-CFTR-mediated chloride transport to more than 10% of that observed in non-cystic fibrosis human bronchial epithelial cultures.
- CFTR chloride channel function is critically required for amiloride-sensitive epithelial sodium channel (ENaC) activation in the native human sweat duct, regardless of phosphorylation and adenosine triphosphate (ATP).
- The data provide novel insight into the subunit composition of the epithelial CFTR/AMPK/NDPK complex, such that: CFTR interacts specifically with AMPK alpha1, gamma2 and NDPK-A and not NDPK-B or AMPK gamma1.
- Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis
- Transgenic CFTR regulates the renal potassium (K) secretory channel by providing a protein kinase A-regulated functional switch that determines the distribution of open and ATP-inhibited K channels in apical membranes
- Analysis of the cystic fibrosis transmembrane regulator gene for exon deletions and duplications should be included for complete study of CBAVD patients, especially those considering assisted reproduction.
- analysis of genomic rearrangements involving deletions in the CFTR gene
- In United Arab Emirates (UAE), pattern of CF causing gene mutations is different than rest of the Arabs in the region and 95% of CF in Emirati families has been found due to two mutations only - -p.S549R(T>G) and p.F508del.
- CRT in the post-endoplasmic reticulum compartments may act as a negative regulator of the cell surface CFTR
- Results suggest that protease-activated receptor stimulation of chloride secretion occurs by an indirect mechanism involving the synthesis and release of prostaglandins and requires activation of CFTR .
- amikacin suppressed the hCFTR-G542X premature stop mutation more effectively than gentamicin when administered at these clinically relevant doses
- Thus PKC-beta2 is hypothesized to participate in the regulation of CFTR apical plasma membrane targeting within the constitutive cellular biosynthetic pathway.
- Finds three novel mutations (M1T, 3121-3C-->G, and L1324P) of CF transmembrane conductance regulator associated with the development of cystic fibrosis.
- valosin-containing protein (VCP) is an integral component of the endoplasmic reticulum associated degradation and cellular stress pathways induced by the unfolded protein response, which destroys the CFTR to cause cystic fibrosis
- The significantly higher frequency of CFTR mutations among patients with chronic pulmonary disease compared with unaffected controls suggests that these mutations may increase risk for disease
- Data indicate that most of patients with Congenital bilateral absence of the vas deferens (CBAVD) have mutations in the CFTR gene.
- Finds a striking linkage disequilibrium between GATT-TUB9 pair and deltaF508 on the CFTR locus suggesting a gene flow between sub-Saharan and Mediterranean groups in Brazil that may result in cystic fibrosis mutations.
- findings show that Rab27a is involved in CFTR channel regulation through protein-protein interactions involving Munc13-4 and SLP-5 effector proteins
- Genetic mutation in the the cystic fibrosis transmembrane conductance regulator has been described to play a role in the development of pancreatitis.
- analysis of mutations (Q98R and Q220X) in the CFTR gene in a Korean cystic fibrosis patient
- The 5T variant of CFTR has a milder clinical consequence than previously estimated in females.
- Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in pancreatic tumour biology and suggest the implication of new signalling pathway(s) in MUC4 regulatio
- Among 20 CFTR-identified alterations, the 5T-12TG haplotype was the second most frequent mutation in hypertrypsinemia in newborns.
- Ability to transport chloride is not critical determinant of regulation of mENaC by activated CFTR in Xenopus oocytes. I148T-CFTR is dysfunctional despite maintaining ability to transport chloride.
- we review what is known about the relationship between extracellular nucleotides and CFTR, the role of extracellular nucleotides in epithelial pathophysiology and their putative role as therapeutic agents--{REVIEW}
- Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508.
- These results support the hypothesis that lack of CFTR activity is responsible for the onset of the inflammatory cascade in the cystic fibrosis lung.
- Cystic fibrosis with homozygous CFTR I1234V mutation is associated with pancreatic sufficiency.
- Derlin-1 recognizes misfolded, nonubiquitylated CFTR to initiate its dislocation and degradation early in the course of CFTR biogenesis, perhaps by detecting structural instability within the first transmembrane domain
- study shows no association between cystic fibrosis transmembrane conductance regulator (CFTR) mutations and pancreatitis and the importance of alpha 1-antitrypsin(AAT) variants remains speculative
- The profile of mutations in the CFTR gene in Latin America, which reflects the heterogeneity of its inhabitants, shows the complexity of the molecular diagnosis of CF mutations in most of the Latin American countries
- Opening of the channel is initiated by ATP binding at the nucleotide binding domain-2 (NBD2) site, whereas separation of the NBD dimer at the NBD1 site constitutes the rate-limiting step in channel closing.
- 1 new nonsense mutation (K536X) in the nucleotide-binding domain 1 (NBD1) region & 2 new missense mutations (Y122H & T338A) in the M2 & M6 regions were found. K536X causes obstructive azoospermia.
- These data demonstrate remarkable and previously unrecognized immobilization of CFTR in the plasma membrane and provide direct evidence that C-terminal coupling to the actin skeleton via EBP50/ezrin is responsible for its immobility.
- relatively high frequency of the DeltaF508 cystic fibrosis mutation in the Greek population
- The quantitative real-time PCR with melting curve analysis is a reliable and fast method for the detection of DeltaF508del.
- Mutations and variations in pancreatitis patients.
- These results indicate that BafA1-sensitive pathway is required for CFTR maturation and emphasize that endosomal trafficking pathway might be involved in the maturation of CFTR.
- the interaction of ASIC3 and CFTR may contribute to defective salt and fluid transepithelial transport in the cystic fibrotic pulmonary system
- CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells
- Calculated upper estimates of activation free energies yielded minimum estimates of activation entropies, allowing reconstruction of the thermodynamic profile of gating, which was qualitatively similar for partially and highly phosphorylated CFTR.
- These results suggest that positively charged arginine residues act to concentrate Cl(-) ions at the inner mouth of the CFTR pore, and that this contributes to maximization of the rate of Cl(-) ion permeation through the pore.
- Butyrate may inhibit, rather than stimulate, the anion secretory capacity of human epithelial cells that express wild-type CFTR, particularly in tissues that normally exhibit robust Ca(2+)-activated secretion.
- These studies implicate a role for N-WASP-mediated actin polymerization in regulating CFTR surface expression and channel activity.
- Data suggest that the revertant mutants G550E and 4RK might rescue F508del-cystic fibrosis transmembrane conductance regulator by distinct mechanisms.
- Patients with a high-risk CFTR genotype had a greater than twofold increased risk of death compared to patients with a low-risk CFTR genotype.
- Hsp90 cochaperones modulate Hsp90-dependent stability of CFTR protein folding in the endoplasmic reticulum
- biochemical analysis of the biosynthetic assembly of CFTR
- CAL is a negative regulator of DeltaF508-CFTR cell-surface expression
- Structurally and functionally intact CFTR NBD-1 in activated CFTR can regulate mENaC surface expression independent of Cl(-) transport in Xenopus oocytes.
- An association between DeltaF508 and Crohn's disease (CD) was observed. DeltaF508 heterozygosity might exert a protective effect in CD.
- Regulates oxidative stress which may, in combination with smoking, increase acquired cystic fibrosis.
- In cells, filamin A tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel.
- Modulation of the expression level of CFTR protein partners, like NHE-RF1, can rescue sequence-deleted CFTR activity.
- In screening, only three mutations were found: deltaF508 mutation was found in 25 (17.8%) alleles, N1303K in six (4.3%) alleles and G542X in five (3.6%) alleles. Thus, a total of 3 mutations cover 25.7% of Cystic fibrosis alleles.
- Compound genetic abnormalities in CFTR mutation patients can be a contributing factor when abnormal spermatogenesis is encountered.
- results support the hypothesis that components of the retrotranslocation machinery such as VCP do not interact with CFTR in epithelial cells that endogenously express wild-type CFTR since under normal conditions processing of WT protein is efficient
- screened primary ciliary dyskinesia/Kartagener syndrome patients and their siblings for the presence of the CFTR mutations that are most frequently found in the Polish population: the severe F508del and 2,3del21kb, and the mild 3849+10kbC > T
- rapid IL-1 release and signaling through IL-1R represent key steps in the innate immune response to P. aeruginosa infection, and this process is deficient in cells lacking functional CFTR.
- CF patients homozygous for the delta F508 mutation have a greater incidence of hypoplastic or underdeveloped sinuses.
- findings demonstrate that the pleiotropic protein kinase CK2 binds wild-type CFTR near F508 and phosphorylates nucleotide-binding domain 1 at Ser-511 in vivo and that mutation of Ser-511 disrupts CFTR channel gating
- identification of CFTR gene rearrangements in congenital bilateral absence of the vas deferens
- 121 disease-causing mutations were identified, accounting for 96% (1,877 out of 1,954) of CF alleles. Specific geographic distributions for the most common mutations, p.F508del, p.G542X, c.1811 + 1.6kbA > G and c.1609delCA, were confirmed.
- Insulin supplementation in diabetic subjects with CFTR deltaF508 mutation is a rational therapy for consideration, although this does not preclude that therapy directed toward insulin resistance may be involved.
- CFTR confers cAMP regulation to CLIC1 activity in the plasma membrane
- CFTR's two ATP-binding pockets play distinct functional roles in gating
- Improved maturation of CFTR mediated by a valine signal may be of potential use in gene therapy of cystic fibrosis.
- the frequencies, symptoms, testing, and reporting of genotypes with the 5T polythymidine tract which reduces splicing efficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (Review)
- Model a RACK1 proteome consisting of PKCepsilon-RACK1-NHERF1-NHERF1-tubulin with a role in stable expression of CFTR in the apical plasma membrane of epithelial cells.
- CFTR mutations and their incidence in the Ecuadorian population were F508del (37.1%), G85E (8.9%), G542X (2.4%), N1303K (2.4%), G551D (1.6%) and R334W (0.8%); we are reporting one of the highest incidences of G85E in the world
- This study found that co-expressed cystic fibrosis transmembrane conductance regulator (CFTR) stabilizes epithelial sodium channel(ENaC) at the plasma membrane, suggesting that CFTR regulates ENaC stability, not just opening.
- gastrointestinal disease in adulthood associated with CFTR mutations [review]
- Identification of large rearrangements further expands the CFTR mutational spectrum in CBAVD
- myosin Vb is required for CFTR recycling in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells
- Absence of CFTR at the cell membrane leads to an intrinsic AP1 and NF-kappa B activity.
- The presence of the Delta F508 homozygous mutation did not alter survival in cystic fibrosis.
- The effect of the R553X mutation on the splicing of exon 11 of the cystic fibrosis transmembrane conductance regulator gene was investigated.
- An analysis of 143 unrelated Belgian patients with a positive diagnosis of cystic fibrosis for mutations in the cystic fibrosis transmembrane conductance regulator gene is presented.
- Mutations/variants in the CFTR gene plus or minus mutations in the SPINK1 gene may confer a high risk for recurrent pancreatitis.
- The P67S mutation reduces CFTR chloride channel function by reducing channel surface expression, however, residual function of the mutant channel is sufficient to prevent the development of severe CF symptoms
- structural impact of cystic fibrosis-phenotypic mutations in the extracellular loop 2 on interactions between the TM3 and TM4 helices of CFTR in constructs containing CFTR residues 194-241
- Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility.
- Models of the first nucleotide-binding domain (NBD1) region of the wild-type and mutant forms of human CFTR were created.
- Two simple Alu insertions were identified in the CFTR(cystic fibrosis transmembrane conductance regulator) gene, within exons 16 and 17b, a previously unknown mechanism causing Cystic Fibrosis
- The 50% reduction in the CF transmembrane conductance regulator protein in heterozygotes is insufficient to cause platelet activation.
- study has demonstrated that carriers of mild mutations of CFTR and a distinct haplotype carry an increased risk of developing idiopathic chronic pancreatitis (ICP) in Chinese; T5 allele is associated with early onset of ICP in our population.
- Interference with Hook2 function alters CFTR aggresome formation.
- a cross-talk between CFTR and a variety of gap junction channels. Cytoskeletal scaffolding proteins and/or other intermediate cytoplasmic proteins are likely to play a role in CFTR-connexins interaction.
- These results show that IL-13 interferes with ion and water channel expression and localization during epithelial regeneration and may thereby influence mucus composition and hydration.
- 15 different mutations were identified which account for 58.5% of the cystic fibrosis chromosomes in an Algerian population
- observations suggest that impaired epithelial ion transport due to mild CFTR genotype (namely, IVS8-5T-TG12) might be involved as a triggering factor in acute onsets of pancreatitis in pancreas divisum, possibly through abnormal pancreatic fluid secretio
- Pre-mRNA secondary structure plays a major role on donor-site usage and splicing efficiency in CFTR pseudoexon inclusion events.
- This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men.
- cAMP-dependent Cl- fluxes through CFTR are involved in the regulation of ENaC during sperm capacitation and thus contribute to the observed hyperpolarization associated with this process
- correction of the abnormal trafficking of F508del-CFTR proteins might have profound consequences on cellular homeostasis such as the control of intracellular Ca(2+) level.
- A kinase-dead SGK mutant (K127N) had a dominant-negative effect on CFTR, reducing CFTR Cl currents by 38%.
- Glutathione and cysteine redox couples in cell lysates and apical fluid were equal in cystic fibrosis and CFTR-corrected cells.
- Protein kinase C phosphorylation disrupts Na+/H+ exchanger regulatory factor 1 autoinhibition and promotes cystic fibrosis transmembrane conductance regulator macromolecular assembly.
- CFTR has a role in beta adrenergic receptor-dependent alveolar fluid clearance.
- Reveals the CFTR gene mutation status in the Croatian population and establishes the haplotypes associated with cystic fibrosis and those associated with specific gene mutations.
- A TG15 T5 gene variant in trans with a cystic fibrosis causing mutation in monozygotic twins.
- haploinsufficiency of GNAS causes a significant reduction in the activation of the downstream target, CFTR, in vivo
- CTFR gene transfer to human cystic fibrosis pancreatic duct cells using a Sendai virus vector.
- The CFTR regulatory region interacts with the nucleotide-binding domain1.
- We identified 37 CFTR mutations in 69 well characterized Iranian CF patients, obtaining a CFTR mutation detection rate of 81.9%, the highest detection rate obtained in the Iranian population so far.
- a testicular factor (genetic or environmental) rather than CFTR gene mutations plays a role in determining the phenotype in congenital absence of the vas deferens
- the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter.
- The detection and characterization of a novel large duplication in the CFTR gene.
- Ex vivo biochemical analysis of rectal biopsies of a carrier of the mild 2789+5 G-A CFTR frameshift splice site mutation revealed mutant truncated CFTR of expected size and an imbalance of more core-glycosylated and less mature full-length CFTR.
- Genotype-phenotype correlation revealed that p.F508del positive patients had a more severe disease, manifesting at an earlier age.
- Our results revealed a total of 25 different CF mutations representing nearly 90% of CF alleles in Brazilian patients.
- There is evidence linking CFTR mutations to primary sclerosing cholangitis.
- There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood primary sclerosing cholangitis.
- Our results indicate that the low expression CFTR polymorphisms may contribute to a reduced risk of prostate cancer in Chinese Han population.
- reveal a novel mechanism for genistein regulation of F508delCFTR, i.e. retention by inhibition of endocytosis
- A new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR.
- Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in heterozygosis with congenital absence of vas deferens
- Following haplotype reconstruction and simulation, the ages were estimated to be approximately 600, 1000, 1200 and 600 years, respectively (with a 95% confidence interval).
- linked the acetylation signature of nucleosomal histones to active intestinal CFTR expression and occupation by transcription factors HNF1alpha, Cdx2 and Tcf4 which converge to modify chromatin architecture
- annexin V is necessary for normal CFTR chloride channel activity.
- analysis of species-dependent differences of CFTR-DeltaF508 in human, pig and mouse
- The analysis of genotype and phenotype in cystic fibrosis showed that frequency and severity of clinical manifestation of the gastrointestinal tract disorders correlates with deltaF508 mutation in CFTR.
- Mutation carrier status was not associated with overall fertility.
- Abnormal fetal lung CFTR protein regulation could give rise to a predisposition to the post-natal inflammatory changes of the airways that characterize CF disease
- corrector molecules promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein
- results place CFTR and ENaC within reach of each other, suggestive of a direct interaction between these two proteins.
- exploit species differences between human and murine CFTR to investigate CFTR channel gating
- Coat protein complex I plays a critical role in CFTR trafficking to the cell membrane in an adenocarcinoma cell line.
- CFTR mutation frequency in pancreatitis patient cohort was 11.2%; in 'idiopathic definitive chronic pancreatitis' patients, frequency was 12.7%; in 'acute pancreatitis' or 'possible chronic pancreatitis' patients frequency was 10% & 9.1%, respectively
- This genetic study is the first one to address the association of HLP with the CFTR mutation/variant/haplotype and TNF promoter polymorphism in a Chinese HTG population. The results suggest that the occurrence of HLP is multifactorial and polygenic.
- These results indicate that NHERF1 plays a role in the turnover of CFTR at the cell surface, and that rDeltaF508 CFTR at the cell surface remains highly susceptible to degradation.
- allele and haplotype frequencies differed greatly between the two populations as well as among Amerindians and normal European Brazilians and European Brazilian cystic fibrosis patients
- The multidrug resistance protein 4 (MRP4), a cAMP transporter, functionally and physically associates with CFTR.
- CFTR is expressed in human bronchiolar and alveolar epithelial cells
- A CISD1-GFP chimera was found to be located into mitochondria.
- The CFTR gene mutations frequency in men with nonobstructive azoospermia, oligozoospermia and asthenozoospermia is similar to those observed in general population.
- analysis of how a human monoclonal antibody fragment specific to the folded conformation of NBD1 of CFTR inhibits the aggregation of NBD1 in vitro
- Conformational changes in a pore-lining helix coupled to cystic fibrosis transmembrane conductance regulator channel gating.(
- A2A receptors open Cl- channels in pancreatic ducts cells with functional cystic fibrosis transmembrane regulator (CFTR).
- pancreatitis seems associated with genetic risk factors such as mutations of the cystic fibrosis gene.
- The researchers investigated the deltaF508 mutation of the CFTR gene and found a lower frequency in this Brazilian population than in the rest of the world.
- These results suggest that low temperature induces the appearance of a mix population of mature and immature CFTR molecules at the plasma membrane through distinct pathways
- The hypothesis aims to the possible role of epithelial ion channels, particularly CFTR involvement, in the pathogenesis of OHSS.
- Mechanism of G551D-CFTR (cystic fibrosis transmembrane conductance regulator) potentiation by a high affinity ATP analog
- CFTR mutations may lead to unusual electrophysiological or clinical manifestations.
- Beta-oestradiol-dependent up-regulation of NHERF1 significantly increases F508CFTR functional expression in CFBE41o(-) cells.
- These results show that bicarbonate-controlled sAC stimulation must be taken into account in cell physiology and that basal CFTR expression depends on an ionic parameter.
- gp78 cooperates with RMA1 with E4-like activity in the ERAD of CFTRDeltaF508.
- Data suggest that GPCR-mediated signaling integrity is maintained after lipid raft disruption in epithelial cells and cast doubts on the role of lipid rafts as signaling platforms in GPCR-mediated signaling.
- DeltaF508 CFTR (cystic fibrosis transmembrane conductance regulator) has much more conformational freedom compared to the wild-type, and exposes its hydrophobic interior to the solution
- Multiplex ligation-dependent probe amplification was performed in 49 patients who still had 1 or 2 unidentified alleles (total of 52 unidentified alleles) after extensive analysis of CFTR gene. We characterized 9 different deletions & a new duplication.
- CFTR rearrangements hve a frequency of about 2-3% in alleles from patients bearing CF in Italian regions.
- role of GTP in the degradation of DeltaF508-CFTR and the alpha subunit of the T-cell receptor (TCRalpha), representative misfolded ER membrane proteins
- analysis of CFTR function [review]
- 3D structure of CFTR, constructed by molecular modeling and supported biochemically, in which Phe-508 mediates a tertiary interaction between the surface of NBD1 and a cytoplasmic loop (CL4) in the C-terminal membrane-spanning domain
- results predict a major impact of the CFTR missense variants analyzed, except p.R75Q, on the cystic fibrosis phenotype and highlight the importance of the CFTR N-terminus on channel physiology
- Both DNA methylation and histone deacetylation contribute to CFTR transcriptional inhibition.
- two mutation panels exceeding 90% sensitivity threshold are now proposed for cystic fibrosis carrier screening in this region
- Data show that polymorphisms of poly-T, TG-repeats, and M470V distribution in CFTR are similar among Asians, but show marked differences in frequency from those single haplotype polymorphisms or linkage haplotypes in Caucasians.
- CFTR-dependent chloride anion transport contributes significantly to killing PsA by normal neutrophils and when defective as in CF, may compromise the ability to clear PsA.
- Cystic fibrosis airway cells expressing DeltaF508-CFTR mutation significantly enhanced P. aeruginosa biofilm formation, and DeltaF508 rescue with wild-type CFTR reduced biofilm formation
- Abnormal CFTR function may be a common cause for recurrent idiopathic pancreatitis.
- The results suggest that correctors interact with CFTR in the ER to promote folding of the protein into a native structure.
- The results of the present study provide evidence that CFTR(inh)-172 interacts directly with CFTR, and that Arg347 is important for the interaction.
- functional CFTR Cl(-) channel activity is crucial for regulation of lung proteasomal degradation and NF-kappaB activity in conditions of oxidative stress.
- nonsteroidal anti-inflammatory drugs increase the function of both wild-type cystic fibrosis transmembrane conductance regulator and the phenylalanine 580 deletion in cultured human airway epithelial cells at endogenous levels of cAMP
- Messenger ribonucleic acid quantification of all known ABC transporters revealed multiple alterations in ABC transporter expression in failing human hearts compared to nonfailing controls. These include a loss of ABCC7 chloride channels
- R352 plays an important structural role in CFTR, perhaps reflecting its involvement in forming a salt bridge with residue D993.
- Computational studies reveal phosphorylation-dependent changes in the unstructured R domain of CFTR.
- A TGFB1 haplotype was highly associated with increased lung function in patients grouped by CFTR genotype.
- The natural coumarin activators of cystic fibrosis transmembrane conductance regulator may represent a new class of natural lead compounds for the development of pharmacological therapies for cystic fibrosis.
- Kinetic studies with labeled linoleic acid demonstrated CF cells increase conversion to longer & more-desaturated fatty acids such as arachidonic acid. CFTR dysfunction is associated with altered fatty acid metabolism in cultured airway epithelial cells.
- overexpression of DeltaF508 CFTR causes ER stress and activates the UPR. UPR activation precedes a marked decrease in endogenous WT CFTR mRNA expression.
- In 128 Romanian patients with CF, the F508del mutation was the most frequent.
- Environmental factors that induce hypoxic signaling regulate CFTR mRNA and epithelial Cl(-) transport in vitro and in vivo
- disruption of the excessive association of the cochaperone, Aha1, with DeltaF508 CFTR is associated with the correction of its maturation, trafficking and regulated anion channel activity in human airway epithelial cells.
- In 7 of 32 cystic fibrosis-affected self-identified Hispanics for whom only one or no mutations were identified by extensive molecular testing, exon deletions appeared to be present with a multiplex ligation-dependent probe amplification (MLPA) assay.
- the human CFTR gene product does not directly mediate oxalate efflux in secretory epithelia and hence is not directly involved in oxalate homeostasis in humans
- the relationship of mutations in the CFTR gene with congenital bilateral absence of the vas deferens and congenital absence of the uterus and vagina (Review)
- Results report that syntaxin 7, syntaxin 8, vti1b and VAMP8 physically and functionally interact with CFTR.
- An atomic model of the outward-facing three-dimensional structure of the membrane-spanning domains (MSDs) and nucleotide-binding domains (NBDs) of human cystic fibrosis transmembrane conductance regulator (CFTR), is described.
- gene therapy target for cystic fibrosis
- Our results represent the first genome-wide screen for CRS and suggest that a locus on 7q31.1-7q32.1 influences disease susceptibility. This may be the CFTR gene or another nearby locus.
- pathobiology of the gastrointestinal and hepatic manifestations of cystic fibrosis disease in relation to their genetic basis in mutations of the CF transmembrane conductance regulator (CFTR) gene [review]
- The CFTR M470V gene variant as a potential modifier of COPD severity in a Serbain population is reported.
- mediation of regulatory signals between cytoplasmic- and membrane-integrated domains of the CFTR channel apparently relies on an array of precise but highly dynamic interdomain structural joints.
- three novel CFTR missense mutations with fatal and clinical symptoms different depending on the mutation detected in Spanish (Galician) patients.
- The role of N-linked glycosylation in the processing of wild-type and DeltaF508 CFTR, is investigated.
- Validation of a high-resolution DNA melting analysis for mutation screening of CTFR gene is reported.
- the NEG2 region at the C terminus of the R domain allows stabilization of CFTR in a regulated intracellular compartment from which it traffics to the plasma membrane in response to cAMP/PKA stimulation
- Case Report: Outcome of intracytoplasmic sperm injection for a couple in which the man is carrier of CFTR p.[R74W;V201M;D1270N] and p.P841R mutations and his spouse a heterozygous carrier of p.F508del mutation of CFTR.
- Patients with Pulmonary nontuberculous mycobacterial infection are taller and leaner and have higher rates of cystic fibrosis transmembrane conductance regulator mutations than control subjects
- disrupt interactions between the nucleotide binding and transmembrane domains of P-glycoprotein and the cystic fibrosis transmembrane conductance regulator
- A dependence on calnexin for proper assembly of CFTR's membrane spanning domains, was identified.
- Three-dimensional reconstruction of human cystic fibrosis transmembrane conductance regulator chloride channel reveals an ellipsoidal structure with orifices beneath the putative transmembrane domain
- CFTR channel is present in ASM cells, and that it modulates the release of Ca(2+) in response to contractile agents.
- CFTR DeltaF508 export requires a local biological folding environment sensitive to heat/stress-inducible factors found in cell types, suggesting that energetic stabilization by reduced temperature is necessary, but not sufficient, for export of DeltaF508
- The phenotypic characteristics of polarized DeltaF508 homozygote CF bronchial epithelial (CFBE41o-) cells were evaluated following transfection with episomal expression vector containing either full-length wild type (wt) and DeltaF508CFTR cDNA.
- Reduced Cl- conductance caused by the three CFTR mutations affects normal development of vas deferens and leads to congenital bilateral absence of vas deferens.
- TNR-CFTR mRNA alternative splicing is probably mediate by splicing pathways utilizing U11 and U12 snRNAs.
- Raised anxA5 expression induces an augmented function of DeltaF508-CFTR due to its increased membrane localization, suggesting that anxA5 is a potential therapeutic target in cystic fibrosis.
- This case is important not only because of the distinct phenotypic abnormality seen with specific CF mutations but also because of the associated genotype.
- The role of hypoxia inducible factor-1 on the expression of cystic fibrosis transmembrane conductance regulator and chloride and water flux in intestinal cells is reported.
- Eight novel mutations were identified in CFTR in Indian Cystic fibrosis patients.
- The F508del and G542X mutations were strongly associated with haplotype B in Mexican cystic fibrosis
- A stabilized form of GADD34 promoted the accumulation and aggregation of the mutant cystic fibrosis transmembrane conductance regulator (CFTRDeltaF508)
- the CFTR gene is implicated in the infertile members of the Cystic fibrosis families.
- Localization studies of rare missense mutations in CFTR helped to correlate disease severity with the functional consequences of amino acid substitutions.
- analysis of a novel CFTR mutation in a Korean infant with cystic fibrosis [case report]
- These results suggest reversal of the IP3R dysfunction in F508del-CFTR epithelial cells by correction of the abnormal trafficking of F508del-CFTR in cystic fibrosis cells.
- Our data suggest that THF acts directly on CFTR to potentiate channel gating, but its efficacy is weak and dependent on the phosphorylation status of CFTR.
- Several CFTR-variants affecting the functional properties of the CFTR protein seem to offer protection against the development of primary sclerosing cholangitis (PSC), confirming our hypothesis that CFTR might be implicated in the pathogenesis of PSC.
- After ingestion of Burkholderia cenocepacia, acidification and phagolysosomal fusion of the bacteria-containing vacuoles occur in a lower percentage of CFTR-negative macrophages than CFTR-positive cells.
- the F508C variant in CFTR protein may represent a pathogenic defect and lead to congenital bilateral absence of the vas deferens when combined with a second cystic fibrosis transmembrane conductance regulator mutation.
- Phenotypic variability in a family with pancreatitis and cystic fibrosis sharing common mild CFTR mutation: report on CFTR mutations and their phenotypic variability.
- These two cases are the first report of cystic fibrosis associated with a delta F508 mutation in a Taiwanese patient attributable to a mutation most commonly seen in Caucasians.