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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 Jun;64(6):1499–1504. doi: 10.1086/302429

Cystic fibrosis as a disease of misprocessing of the cystic fibrosis transmembrane conductance regulator glycoprotein.

J R Riordan 1
PMCID: PMC1377893  PMID: 10330337

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Selected References

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  1. Aridor M., Weissman J., Bannykh S., Nuoffer C., Balch W. E. Cargo selection by the COPII budding machinery during export from the ER. J Cell Biol. 1998 Apr 6;141(1):61–70. doi: 10.1083/jcb.141.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown C. R., Hong-Brown L. Q., Biwersi J., Verkman A. S., Welch W. J. Chemical chaperones correct the mutant phenotype of the delta F508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones. 1996 Jun;1(2):117–125. doi: 10.1379/1466-1268(1996)001<0117:ccctmp>2.3.co;2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casals T., Pacheco P., Barreto C., Giménez J., Ramos M. D., Pereira S., Pinheiro J. A., Cobos N., Curvelo A., Vázquez C. Missense mutation R1066C in the second transmembrane domain of CFTR causes a severe cystic fibrosis phenotype: study of 19 heterozygous and 2 homozygous patients. Hum Mutat. 1997;10(5):387–392. doi: 10.1002/(SICI)1098-1004(1997)10:5<387::AID-HUMU9>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  4. Chang X. B., Hou Y. X., Riordan J. R. ATPase activity of purified multidrug resistance-associated protein. J Biol Chem. 1997 Dec 5;272(49):30962–30968. doi: 10.1074/jbc.272.49.30962. [DOI] [PubMed] [Google Scholar]
  5. Cheng S. H., Gregory R. J., Marshall J., Paul S., Souza D. W., White G. A., O'Riordan C. R., Smith A. E. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell. 1990 Nov 16;63(4):827–834. doi: 10.1016/0092-8674(90)90148-8. [DOI] [PubMed] [Google Scholar]
  6. Clement J. P., 4th, Kunjilwar K., Gonzalez G., Schwanstecher M., Panten U., Aguilar-Bryan L., Bryan J. Association and stoichiometry of K(ATP) channel subunits. Neuron. 1997 May;18(5):827–838. doi: 10.1016/s0896-6273(00)80321-9. [DOI] [PubMed] [Google Scholar]
  7. Cosson P., Letourneur F. Coatomer (COPI)-coated vesicles: role in intracellular transport and protein sorting. Curr Opin Cell Biol. 1997 Aug;9(4):484–487. doi: 10.1016/s0955-0674(97)80023-3. [DOI] [PubMed] [Google Scholar]
  8. Dalemans W., Barbry P., Champigny G., Jallat S., Dott K., Dreyer D., Crystal R. G., Pavirani A., Lecocq J. P., Lazdunski M. Altered chloride ion channel kinetics associated with the delta F508 cystic fibrosis mutation. Nature. 1991 Dec 19;354(6354):526–528. doi: 10.1038/354526a0. [DOI] [PubMed] [Google Scholar]
  9. Denning G. M., Anderson M. P., Amara J. F., Marshall J., Smith A. E., Welsh M. J. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature. 1992 Aug 27;358(6389):761–764. doi: 10.1038/358761a0. [DOI] [PubMed] [Google Scholar]
  10. Drumm M. L., Wilkinson D. J., Smit L. S., Worrell R. T., Strong T. V., Frizzell R. A., Dawson D. C., Collins F. S. Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes. Science. 1991 Dec 20;254(5039):1797–1799. doi: 10.1126/science.1722350. [DOI] [PubMed] [Google Scholar]
  11. Gilbert A., Jadot M., Leontieva E., Wattiaux-De Coninck S., Wattiaux R. Delta F508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells. Exp Cell Res. 1998 Jul 10;242(1):144–152. doi: 10.1006/excr.1998.4101. [DOI] [PubMed] [Google Scholar]
  12. Jensen T. J., Loo M. A., Pind S., Williams D. B., Goldberg A. L., Riordan J. R. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell. 1995 Oct 6;83(1):129–135. doi: 10.1016/0092-8674(95)90241-4. [DOI] [PubMed] [Google Scholar]
  13. Jiang C., Fang S. L., Xiao Y. F., O'Connor S. P., Nadler S. G., Lee D. W., Jefferson D. M., Kaplan J. M., Smith A. E., Cheng S. H. Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am J Physiol. 1998 Jul;275(1 Pt 1):C171–C178. doi: 10.1152/ajpcell.1998.275.1.C171. [DOI] [PubMed] [Google Scholar]
  14. Johnston J. A., Ward C. L., Kopito R. R. Aggresomes: a cellular response to misfolded proteins. J Cell Biol. 1998 Dec 28;143(7):1883–1898. doi: 10.1083/jcb.143.7.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kartner N., Augustinas O., Jensen T. J., Naismith A. L., Riordan J. R. Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland. Nat Genet. 1992 Aug;1(5):321–327. doi: 10.1038/ng0892-321. [DOI] [PubMed] [Google Scholar]
  16. Loo M. A., Jensen T. J., Cui L., Hou Y., Chang X. B., Riordan J. R. Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J. 1998 Dec 1;17(23):6879–6887. doi: 10.1093/emboj/17.23.6879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Loo T. W., Clarke D. M. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators. J Biol Chem. 1997 Jan 10;272(2):709–712. doi: 10.1074/jbc.272.2.709. [DOI] [PubMed] [Google Scholar]
  18. Lukacs G. L., Mohamed A., Kartner N., Chang X. B., Riordan J. R., Grinstein S. Conformational maturation of CFTR but not its mutant counterpart (delta F508) occurs in the endoplasmic reticulum and requires ATP. EMBO J. 1994 Dec 15;13(24):6076–6086. doi: 10.1002/j.1460-2075.1994.tb06954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meacham G. C., Lu Z., King S., Sorscher E., Tousson A., Cyr D. M. The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. EMBO J. 1999 Mar 15;18(6):1492–1505. doi: 10.1093/emboj/18.6.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nichols W. C., Ginsburg D. From the ER to the golgi: insights from the study of combined factors V and VIII deficiency. Am J Hum Genet. 1999 Jun;64(6):1493–1498. doi: 10.1086/302433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nishimura N., Balch W. E. A di-acidic signal required for selective export from the endoplasmic reticulum. Science. 1997 Jul 25;277(5325):556–558. doi: 10.1126/science.277.5325.556. [DOI] [PubMed] [Google Scholar]
  22. Pind S., Riordan J. R., Williams D. B. Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J Biol Chem. 1994 Apr 29;269(17):12784–12788. [PubMed] [Google Scholar]
  23. Prince L. S., Workman R. B., Jr, Marchase R. B. Rapid endocytosis of the cystic fibrosis transmembrane conductance regulator chloride channel. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5192–5196. doi: 10.1073/pnas.91.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Qu B. H., Strickland E. H., Thomas P. J. Localization and suppression of a kinetic defect in cystic fibrosis transmembrane conductance regulator folding. J Biol Chem. 1997 Jun 20;272(25):15739–15744. doi: 10.1074/jbc.272.25.15739. [DOI] [PubMed] [Google Scholar]
  25. Qu B. H., Thomas P. J. Alteration of the cystic fibrosis transmembrane conductance regulator folding pathway. J Biol Chem. 1996 Mar 29;271(13):7261–7264. doi: 10.1074/jbc.271.13.7261. [DOI] [PubMed] [Google Scholar]
  26. Seibert F. S., Linsdell P., Loo T. W., Hanrahan J. W., Clarke D. M., Riordan J. R. Disease-associated mutations in the fourth cytoplasmic loop of cystic fibrosis transmembrane conductance regulator compromise biosynthetic processing and chloride channel activity. J Biol Chem. 1996 Jun 21;271(25):15139–15145. doi: 10.1074/jbc.271.25.15139. [DOI] [PubMed] [Google Scholar]
  27. Seibert F. S., Linsdell P., Loo T. W., Hanrahan J. W., Riordan J. R., Clarke D. M. Cytoplasmic loop three of cystic fibrosis transmembrane conductance regulator contributes to regulation of chloride channel activity. J Biol Chem. 1996 Nov 1;271(44):27493–27499. doi: 10.1074/jbc.271.44.27493. [DOI] [PubMed] [Google Scholar]
  28. Seibert F. S., Loo T. W., Clarke D. M., Riordan J. R. Cystic fibrosis: channel, catalytic, and folding properties of the CFTR protein. J Bioenerg Biomembr. 1997 Oct;29(5):429–442. doi: 10.1023/a:1022478822214. [DOI] [PubMed] [Google Scholar]
  29. Sommer T., Wolf D. H. Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB J. 1997 Dec;11(14):1227–1233. doi: 10.1096/fasebj.11.14.9409541. [DOI] [PubMed] [Google Scholar]
  30. Sun H., Molday R. S., Nathans J. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J Biol Chem. 1999 Mar 19;274(12):8269–8281. doi: 10.1074/jbc.274.12.8269. [DOI] [PubMed] [Google Scholar]
  31. Teasdale R. D., Jackson M. R. Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus. Annu Rev Cell Dev Biol. 1996;12:27–54. doi: 10.1146/annurev.cellbio.12.1.27. [DOI] [PubMed] [Google Scholar]
  32. Thomas P. J., Shenbagamurthi P., Sondek J., Hullihen J. M., Pedersen P. L. The cystic fibrosis transmembrane conductance regulator. Effects of the most common cystic fibrosis-causing mutation on the secondary structure and stability of a synthetic peptide. J Biol Chem. 1992 Mar 25;267(9):5727–5730. [PubMed] [Google Scholar]
  33. Ward C. L., Kopito R. R. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J Biol Chem. 1994 Oct 14;269(41):25710–25718. [PubMed] [Google Scholar]
  34. Ward C. L., Omura S., Kopito R. R. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell. 1995 Oct 6;83(1):121–127. doi: 10.1016/0092-8674(95)90240-6. [DOI] [PubMed] [Google Scholar]
  35. Xiong X., Chong E., Skach W. R. Evidence that endoplasmic reticulum (ER)-associated degradation of cystic fibrosis transmembrane conductance regulator is linked to retrograde translocation from the ER membrane. J Biol Chem. 1999 Jan 29;274(5):2616–2624. doi: 10.1074/jbc.274.5.2616. [DOI] [PubMed] [Google Scholar]
  36. Yang Y., Janich S., Cohn J. A., Wilson J. M. The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9480–9484. doi: 10.1073/pnas.90.20.9480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zerangue N., Schwappach B., Jan Y. N., Jan L. Y. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron. 1999 Mar;22(3):537–548. doi: 10.1016/s0896-6273(00)80708-4. [DOI] [PubMed] [Google Scholar]
  38. Zhang F., Kartner N., Lukacs G. L. Limited proteolysis as a probe for arrested conformational maturation of delta F508 CFTR. Nat Struct Biol. 1998 Mar;5(3):180–183. doi: 10.1038/nsb0398-180. [DOI] [PubMed] [Google Scholar]

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