ライフサイエンスコーパス: CFTR

1 ibrosis transmembrane conductance regulator (CFTR).

2 ibrosis transmembrane conductance regulator (CFTR).

3 ibrosis transmembrane conductance regulator (CFTR).

4 tiation of translation were detected in E60X-CFTR.

5 ide improves the function of rescued F508del-CFTR.

6 an effect absent in mice lacking pendrin or CFTR.

7 her ATP-binding cassette proteins as well as CFTR.

8 location of SLC26A9 and its relationship to CFTR.

9 nd potentiators that recover the function of CFTR.

10 evels of glucocorticoids to activate PKA and CFTR.

11 so partially restores folding of full-length CFTR.

12 ional adaptability of TM helical segments in CFTR.

13 acological compounds interact with and alter CFTR.

14 d by mutations of CF transmembrane receptor (CFTR) - a chloride channel present at the surface of epi

15 In the pancreas, CFTR abnormality results in abnormally viscous secretion

16 CFTR activation by CDCA primarily involved Ca(2+) signal

17 Unlike when phosphorylation happens, CFTR activation by PKA binding is completely reversible.

18 These results implicate CFTR activation in the colon as a major prosecretory mec

19 reatment results in long-term improvement in CFTR activity in hBE cells, as demonstrated by a recover

20 Increases in CFTR activity resulted in increased E-cadherin forces, i

21 Changes in CFTR activity resulted in pressure and/or volume changes

22 Strikingly, increasing CFTR activity was sufficient to block EMT.

23 thelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor.

24 s the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF.

25 with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding

26 h protein is functional with E60X- and G542X-CFTR, although abundant N-terminus truncated proteins du

27 uing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile.

28 chemical interventions that rescue DeltaF508-CFTR and also re-analyzed public datasets characterizing

29 that a rat expressing a humanized version of CFTR and harboring the ivacaftor-sensitive variant G551D

30 helia via a mechanism that is independent of CFTR and is therefore independent of genotype.

31 verexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where

32 orylation-dependent potentiation of wildtype CFTR and other variants also was observed in epithelial

33 ss basolateral secretin receptors and apical CFTR and pendrin.

34 eveloped: correctors that improve folding of CFTR and potentiators that recover the function of CFTR.

35 the therapeutic efficacy of drugs targeting CFTR and provides a value that is in much better agreeme

36 pithelium, more than one cell type expresses CFTR and the molecular mechanisms controlling its transc

37 mediated effects were partially dependent on CFTR and the TRPC6 channel.

38 ibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC).

39 ibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement

40 cations for pharmacological rescue of mutant CFTR, and insights into how CFTR dysfunction impairs key

41 alogues determine the fates of WT and mutant CFTRs, and they suggest that a paralogue switch during b

42 ibrosis Transmembrane Conductance Regulator (CFTR) anion channel is essential for epithelial salt-wat

43 ibrosis transmembrane conductance regulator (CFTR) anion channels produced submucosal gland mucus tha

44 (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ ma

45 In this study, we used CFTR as a model system to investigate the positional eff

46 ibrosis transmembrane conductance regulator (CFTR) associated with a severe form of cystic fibrosis (

47 xpression of CFTR is negatively regulated by CFTR-associated ligand (CAL).

48 CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathw

49 gradation threefold and stabilized mature WT CFTR at the plasma membrance.

50 letely or partially remove the C-terminus of CFTR at the same time as keeping an intact NBD2 (i.e. D1

51 is (CF) transmembrane conductance regulator (CFTR) at the apical membranes of epithelial cells have n

52 , which increased wild-type (WT) and F508del CFTR biogenesis in CFBE airway cells.

53 y 40-50%, suggesting a physiological role in CFTR biogenesis.

54 thelial cells (pHBEs) homozygous for F508del-CFTR but not in non-CF pHBEs, suggesting that F508del-CF

55 anding of the molecular (patho)physiology of CFTR, but also infer therapeutic strategies for differen

56 ncement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling throu

57 endogenous ubiquitin conjugation to F508del CFTR by ~50% and blocked the impact of RNF4 on mutant CF

58 One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 kb C>T), which creates a ne

59 We test an ASO targeting the CFTR c.3718-2477C>T mutation and show that it effectivel

60 We previously showed that inhibition of the CFTR/CAL interaction with a cell-permeable peptide impro

61 l for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).Objectives

62 n the Clinical and Functional Translation of CFTR (CFTR2) project.

63 ed to changes in the open probability of the CFTR channel during exercise, resulting in a decrease in

64 ent approaches--an ATP analog that can drive CFTR channel gating but is unsuitable for phosphotransfe

65 retion of chloride ions, most notably by the CFTR channel, which has been suggested to establish pres

66 pair and complete functional recovery of the CFTR channel.

67 ylatable serines--that PKA efficiently opens CFTR channels through simple binding, under conditions t

68 Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many a

69 Increases in CFTR chloride secretion also induced YAP signaling and c

70 is (CF) transmembrane conductance regulator (CFTR) chloride channel has been argued to be critical fo

71 the CF transmembrane conductance regulator (CFTR) chloride channel.

72 The immature glycoforms of SLC26A9 and CFTR co-immunoprecipitated, consistent with their intera

73 ibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO(3)(-) and Cl(-) secretio

74 t laboratories failed to demonstrate F508del-CFTR correction by Talpha-1.

75 and infection in CF airways independently of Cftr correction.

76 ion, and immunofluorescence, concordant with CFTR correction.

77 have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fib

78 Finally, we found that C18, an analog of the CFTR corrector compound Lumacaftor, induces almost no tr

79 F508del CFTR correctors induced Nrf2 nuclear translocation, Nrf2

80 Here we report that approved F508del CFTR correctors VX809/VX661 recover diminished Nrf2 func

81 xt evaluated whether Rpl12-corrected F508del-CFTR could be further enhanced with concomitant pharmaco

82 f CF but does not replicate a human-relevant CFTR (cystic fibrosis transmembrane conductance regulato

83 covery that CF is caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulato

84 Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulato

85 Rationale: Enhancing non-CFTR (cystic fibrosis transmembrane conductance regulato

86 iver an essential cargo for lumen formation, CFTR (cystic fibrosis transmembrane conductance regulato

87 hich was reduced by ~70% by (R)-BPO-27 or in CFTR-deficient mice.

88 ibrosis transmembrane conductance regulator (CFTR) degradation is initiated by Hsp27, which cooperate

89 ort of neosynthesized E-cadherin, MMP14, and CFTR DeltaF508, three proteins whose exocytosis is sensi

90 the read-through proteins of E60X- and G542X-CFTR demonstrated that both mutations have a single-chan

91 apid internalization of CFTR is dependent on CFTR dephosphorylation by calcineurin, a protein phospha

92 R threefold and doubled expression of mature CFTR, detected by biochemical and functional assays.

93 rough in the development of highly effective CFTR-directed therapeutics, now applicable for up to 90%

94 50% and blocked the impact of RNF4 on mutant CFTR disposal.

95 rescue of mutant CFTR, and insights into how CFTR dysfunction impairs key host defense mechanisms, su

96 d mouse and human model systems to show that CFTR dysfunction in platelets increased calcium entry th

97 We conclude that CFTR dysfunction in platelets produces aberrant TRPC6-de

98 erexpression of beta-ENaC, in the absence of CFTR dysfunction, increased NLRP3-mediated inflammation,

99 not in non-CF pHBEs, suggesting that F508del-CFTR enhances proteasomal SLC26A9 degradation.

100 that DNAJB9 may be a rate-limiting factor in CFTR ERAD pathway.

101 ibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum.

102 Loss of either site extinguished CFTR expression and abolished long-range interactions be

103 emonstrate the utility of ASOs in correcting CFTR expression and channel activity in a manner expecte

104 PIAS4 knockdown reduced WT and F508del CFTR expression by 40-50%, suggesting a physiological ro

105 ibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to pha

106 the lifetime of patients with CF; male sex, CFTR F508del homozygosity, and history of meconium ileus

107 tors for CFLD and severe CFLD were male sex, CFTR F508del homozygosity, and history of meconium ileus

108 to treat cystic fibrosis effectively rescue CFTR function and markedly ameliorate the pathology of c

109 Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interacti

110 Methods: CFTR function assigned to 226 unique CFTR genotypes was

111 (R)-roscovitine also increased MDM CFTR function compared to tezacaftor/ivacaftor treatment

112 strate that sufficient modulation of F508del CFTR function corrects Nrf2 dysfunction in CF.

113 Here we show that defective CFTR function in PDECs directly reduced insulin secretio

114 ulator therapy showed partial restoration of CFTR function in platelets, which may be a convenient ap

115 iators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants.

116 F-causing mutations, partially restoring the CFTR function in terms of protein processing and/or chan

117 These data demonstrate that loss of CFTR function may predispose patients to experience depr

118 Modest increases in CFTR function related to differing genotypes were associ

119 Cs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentia

120 employ HIOs generated in this way to measure CFTR function using cystic fibrosis patient-derived iPSC

121 ulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cyst

122 1 was able to accelerate clearance both when CFTR function was reduced by administration of a pharmac

123 een identified to partially rescue DeltaF508-CFTR function yet remain poorly understood.

124 s, in addition to their ability to stimulate CFTR function, which could contribute to improved clinic

125 and enhances mucus clearance independent of CFTR function.

126 vealed heterogenous effects of these PTCs on CFTR function.

127 CF combination therapies restoring Phe508del-CFTR function.

128 the cystic fibrosis transmembrane regulator (CFTR) function in patient-specific primary epithelial ce

129 ibrosis Transmembrane Conductance Regulator (CFTR) function in vivo in light of recent therapeutic de

130 The discovery of the CFTR gene in the late 1980s triggered a surge of basic r

131 The CFTR gene lies within an invariant topologically associa

132 cted the correlation between mild and severe CFTR gene mutation types and lipid profiles, suggesting

133 the lens of prior knowledge, we compiled a "CFTR Gene Set Library" from literature.

134 mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice site

135 the CF transmembrane conductance regulator (CFTR) gene, a cyclic Adenosine MonoPhosphate (cAMP)-depe

136 the CF transmembrane conductance regulator (CFTR) gene, encoding an anion channel that conducts chlo

137 ibrosis transmembrane conductance regulator (CFTR) gene, encoding for a chloride ion channel.

138 the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infectio

139 ibrosis Transmembrane Conductance Regulator (CFTR) gene.

140 ibrosis transmembrane conductance regulator (CFTR) gene.

141 from the CFTR2-derived relationship between CFTR genotype function and phenotype.

142 Measurements and Main Results: CFTR genotype function exhibited a logarithmic relations

143 tus, age at CFLD and severe CFLD onset, sex, CFTR genotype, history of meconium ileus, treatment with

144 ethods: CFTR function assigned to 226 unique CFTR genotypes was correlated with the clinical data of

145 ibrosis transmembrane conductance regulator (CFTR) have distinct effects on nascent polypeptides.

146 nished Nrf2 function and colocalization with CFTR in CF human primary bronchial epithelia by proximit

147 cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S.

148 We found that deletion of CFTR in platelets produced exaggerated acute lung inflam

149 n CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune

150 of DNAJB9 is sufficient to rescue DeltaF508-CFTR in vitro and in vivo, suggesting that DNAJB9 may be

151 ibrosis transmembrane conductance regulator (CFTR) in urinary HCO(3) (-)excretion and applied it in t

152 ongenetic, CF-like sheep model, ewes inhaled CFTR(inh)172 and neutrophil elastase for 3 days, which r

153 CFTR inhibition has a rapid impact on islet area and ins

154 upport the potential therapeutic efficacy of CFTR inhibition in bile acid-associated diarrheas.

155 Short-term CFTR inhibition increased blood glucose concentrations o

156 We investigated whether short-term CFTR inhibition was sufficient to impact islet morpholog

157 thermore, our data uncover a conformation of CFTR, involving detachment of NBD1 from the transmembran

158 the first time, this study demonstrates that CFTR ion channel function and normal epithelial phenotyp

159 can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to

160 In cells CFTR is activated through the cAMP signaling pathway, ov

161 Furthermore, the rapid internalization of CFTR is dependent on CFTR dephosphorylation by calcineur

162 Here, we found that proper maturation of CFTR is dependent on cross-talk between phosphorylation

163 Here, we show that in normal mice CFTR is located within the cells and also at the apical

164 F508del-CFTR is misfolded and prematurely degraded.

165 Membrane expression of CFTR is negatively regulated by CFTR-associated ligand (

166 that the reduced open probability in Q1412X-CFTR is the result of a disruption of the function of th

167 ibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development o

168 ibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a ke

169 ibrosis transmembrane conductance regulator (CFTR) is an apical membrane anion channel that is widely

170 ibrosis transmembrane conductance regulator (CFTR) is an ion channel protein that is defective in ind

171 ibrosis transmembrane-conductance regulator (CFTR) is largely unknown.

172 ibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunc

173 tion 508, the most common CF-causing mutant)-CFTR, knockdown of DNAJB9 by siRNA increased their expre

174 A Cftr knockout (Cftr KO) mouse expressing mutants of huma

175 In collecting ducts in CFTR knockout mice, baseline pendrin activity was signif

176 tor (CFTR) mutation, whereas the second is a CFTR knockout model.

177 A Cftr knockout (Cftr KO) mouse expressing mutants of human CFTR would ad

178 rtant to elucidate how mutational defects in CFTR lead to its impairment and how pharmacological comp

179 CS exposure also inhibits CFTR, leading to the decreased anion secretion/hydration

180 Cystic fibrosis (CF), caused by mutations to CFTR, leads to severe and progressive lung disease.

181 ial cells, and significantly impaired apical CFTR levels in response to forskolin.

182 tingly, only protein processing of DeltaY512-CFTR, like that of DeltaF508-CFTR, was greatly improved

183 Further analysis revealed that a wild-type CFTR-like PTM pattern and function was restored in Delta

184 a as a key activator of airway expression of CFTR, likely through occupancy at this CRE and the gene

185 regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2

186 CFTR loss of function in mouse or human platelets result

187 based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective auto

188 residues from positions 503 to 513 impaired CFTR maturation.

189 t CDNs containing adenosine induced a robust CFTR-mediated chloride secretory response together with

190 Inhibition of CFTR-mediated intestinal chloride secretion as potential

191 stimulation of which during cholera leads to CFTR-mediated intestinal salt-water loss.

192 nhances other macrophage functions including CFTR-mediated ion efflux.

193 ulti-DDM to assess the efficacy of different CFTR-modulating drugs in human airway epithelial cells d

194 Mechanistically, F508del-CFTR modulation restored Nrf2 phosphorylation and its in

195 This study demonstrates that these CFTR modulator combinations have potent anti-inflammator

196 tezacaftor/ivacaftor and/or the alternative CFTR modulator cysteamine.

197 In patients, treatment with the CFTR modulator drug lumacaftor-ivacaftor increased the r

198 ts before and after treatment with the novel CFTR modulator drug, lumacaftor-ivacaftor.

199 nsight may greatly facilitate assessments of CFTR modulator efficacy in individual patients.

200 minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.

201 cepacia was enhanced by combination with the CFTR modulator tezacaftor/ivacaftor and/or the alternati

202 CF subjects receiving CFTR modulator therapy showed partial restoration of CFT

203 concentration and lung function reported in CFTR modulator trials were compared with function-phenot

204 lly corrected by low temperature or with the CFTR modulator VX-809.

205 However, CFTR modulators approved for use to date are highly expe

206 Here we show that CFTR modulators down regulate this exaggerated proinflam

207 CFTR modulators have been reported to address the basic

208 therapeutic implementation of pharmacologic CFTR modulators have renewed the field's focus on develo

209 ples from patients undergoing treatment with CFTR modulators including ivacaftor, lumacaftor, and tez

210 (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor.

211 f the functional protein studied responds to CFTR modulators like GLPG1837 and Lumacaftor.

212 ine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes.

213 nt G551D could be used to test the impact of CFTR modulators on pathophysiologic development and corr

214 -roscovitine are greatest when combined with CFTR modulators or cysteamine, justifying further clinic

215 cal studies of these three PTCs with various CFTR modulators suggest position-dependent therapeutic s

216 se and the extent of pathology reversal with CFTR modulators.

217 d to augment phagocytosis in the presence of CFTR modulators.

218 proach to monitoring biological responses to CFTR modulators.

219 ibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR

220 ssay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences

221 hybridization and quantitative PCR to assess CFTR mRNA expression in the lungs, immunohistochemistry

222 s unsuitable for phosphotransfer by PKA, and CFTR mutants lacking phosphorylatable serines--that PKA

223 escue CFTR function in some minimal function CFTR mutants.

224 r efficiently improves maturation of various CFTR mutants.

225 PSC lines before and after correction of the CFTR mutation, demonstrating their future potential for

226 508) CF transmembrane conductance regulator (CFTR) mutation, whereas the second is a CFTR knockout mo

227 The 3272-26A>G and 3849+10kbC>T CFTR mutations alter the correct splicing of the CFTR ge

228 To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-asso

229 CFTR mutations cause cystic fibrosis, a lethal incurable

230 uid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF).

231 efitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models.

232 cular defects caused by different classes of CFTR mutations, implications for pharmacological rescue

233 o 90% of people with CF who carry responsive CFTR mutations, including those with just a single copy

234 odulators correct the basic defect caused by CFTR mutations.

235 f VX-770 to CF patients bearing ultra-orphan CFTR mutations.

236 teroids from MYO5B(P663L) piglets maintained CFTR on apical membranes, like tissues from control pigs

237 , treatments with two drug classes targeting CFTR-one boosting ion-channel function (potentiators) an

238 rized and compared the core components of wt-CFTR- or rPhe508del-containing macromolecular complexes

239 The oldest CFTR ortholog identified is from dogfish shark, which re

240 In the airways, CFTR plays an important role in fluid homeostasis and he

241 ibrosis transmembrane conductance regulator (CFTR) plays in platelet-related inflammation.

242 esults should be considered in campaigns for CFTR potentiator discovery, and may enable the expansion

243 The CFTR potentiator ivacaftor is suggested to improve gluco

244 Notably, CFTR potentiators used to treat cystic fibrosis effectiv

245 g a new chemotype to the existing classes of CFTR potentiators.

246 We discover a specialized role of the Stx17-CFTR protein complex that is critical to prevent defecti

247 the premature termination codon (PTC) on the CFTR protein function.

248 the lungs, immunohistochemistry to localize CFTR protein in the airways, and histopathologic assessm

249 ng a two-dimensional characterization of the CFTR protein, it could better inform development of sing

250 ecent therapeutic developments targeting the CFTR protein.

251 ibrosis Transmembrane Conductance Regulator (CFTR) protein.

252 st the presence of both C-terminus truncated CFTR proteins that are poorly functional and read-throug

253 antly enhance the overall function of Q1412X-CFTR provides the conceptual basis for the treatment of

254 hods: In this study, we describe a humanized-CFTR rat expressing the G551D variant obtained by zinc f

255 In particular, the CFTR(-/-) rat has revealed insights into the airway mucu

256 ibrosis transmembrane conductance regulator (CFTR), reduces cyst growth.

257 The results suggest two levels of CFTR regulation in cells: irreversible through phosphory

258 hree PTC mutations, E60X-, G542X- and W1282X-CFTR revealed heterogenous effects of these PTCs on CFTR

259 ibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells(1,2).

260 r of both pulmonary neuroendocrine cells and CFTR-rich ionocytes.

261 e previously reported that rescued Phe508del-CFTR (rPhe508del) can be retained at the cell surface by

262 the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transp

263 tation, E217G, located in the loop region of CFTR's membrane-spanning domain.

264 ing a helical-hairpin construct derived from CFTR's transmembrane (TM) helices 3 and 4 (TM3/4) and th

265 the use of EphaGen in context of BRCA1/2 and CFTR sequencing in a series of 14 runs across 43 blood s

266 ibrosis transmembrane conductance regulator (CFTR), should reduce fluid secretion into the intestinal

267 Colocalizing with CFTR, SLC26A9 has been proposed as a target for the trea

268 One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 k

269 12 depletion significantly increased F508del-CFTR steady-state expression, interdomain assembly, and

270 Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug ac

271 Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interaction impairs bacterial clearance.

272 vestigations of the gating deficit in Q1412X-CFTR suggest that the reduced open probability in Q1412X

273 TR, whose PTC is closer to the C-terminus of CFTR, suggest the presence of both C-terminus truncated

274 iant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation

275 Mutations in the ion channel CFTR that impair its folding and subsequent localization

276 We monitor F508del-CFTR, the most common CF-causing variant, and confirm re

277 For G542X- and E60X-CFTR, the only mechanism capable of generating functiona

278 PIAS4 increased immature CFTR threefold and doubled expression of mature CFTR, de

279 t common CF-associated CFTR variant, F508del-CFTR, through mechanisms that remain incompletely unders

280 r, where Rab11-associated vesicles transport CFTR to aid in lumen establishment.

281 Here, we report that CS causes CFTR to be internalized in a clathrin/dynamin-dependent

282 ion is followed by retrograde trafficking of CFTR to the endoplasmic reticulum.

283 ections to genes with established effects on CFTR trafficking and function and suggested novel roles

284 al SLC26A9 expression increased when F508del-CFTR trafficking was partially corrected by low temperat

285 , an autophagic SNARE protein interacts with CFTR under nutritional stress and bacterial infection an

286 The most common mutant, DeltaF508-CFTR, undergoes proteasomal degradation, extinguishing i

287 ing the phenylalanine 508 deletion (F508del) CFTR variant as well as the over 2000 CF-associated vari

288 s that express the most common CF-associated CFTR variant, F508del-CFTR, through mechanisms that rema

289 de functional correction of Class II and III CFTR variants, restoring cell surface chloride channel a

290 n the trafficking and function of a panel of CFTR variants.

291 cantly restore channel activity for multiple CFTR variants.

292 ration of a pharmacological blocker and when CFTR was fully functional.Conclusions: Enhancing the act

293 ycystic kidney disease (pkd1)-knockout mice, CFTR was located at the plasma membrane, consistent with

294 ng of DeltaY512-CFTR, like that of DeltaF508-CFTR, was greatly improved by low-temperature culture at

295 ttern and function was restored in DeltaF508 CFTR when cells were cultured at 28 degrees C but only i

296 CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine

297 ibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory

298 Electrophysiological studies of W1282X-CFTR, whose PTC is closer to the C-terminus of CFTR, sug

299 the CF transmembrane conductance regulator (CFTR), with approximately 90% of patients harboring at l

300 (Cftr KO) mouse expressing mutants of human CFTR would advance in vivo testing of new modulators.