Molecular chaperones as targets to circumvent the CFTR defect in cystic fibrosis

Frontiers in Pharmacology

Volumn 3 JUL, Issue , 2012, Pages

  Chanoux, Rebecca A ^a   Rubenstein, Ronald C ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

CFTR; Chaperone; Endoplasmic reticulum; ERAD; Heat shock protein; Phenylbutyrate

Indexed keywords

15 DEOXYSPERGUALIN; APOPTAZOLE; CALNEXIN; CHAPERONE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GELDANAMYCIN; HEAT SHOCK COGNATE PROTEIN 70; HEAT SHOCK COGNATE PROTEIN 70 INHIBITOR; MATRINE; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; BIOGENESIS; BRONCHUS MUCOSA; CARBOXY TERMINAL SEQUENCE; CYSTIC FIBROSIS; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; HUMAN; IMMUNOPRECIPITATION; LUNG FIBROSIS; NONHUMAN; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN SYNTHESIS; PROTEIN TARGETING; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; UBIQUITINATION;

EID: 84866180204     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2012.00137     Document Type: Article

References (108)

1. Alberti, S., Bohse, K., Arndt, V., Schmitz, A., and Hohfeld, J. (2004). The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell 15, 4003-4010.
2. Aquino, D. A., Lopez, C., and Farooq, M. (1996). Antisense oligonucleotide to the 70-kDa heat shock cognate protein inhibits synthesis of myelin basic protein. Neurochem. Res. 21, 417-422.
3. Arndt, V., Daniel, C., Nastainczyk, W., Alberti, S., and Hohfeld, J. (2005). BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP. Mol. Biol. Cell 16, 5891-5900.
4. Ashlock, M. A., and Olson, E. R. (2011). Therapeutics development for cystic fibrosis: a successful model for a multisystem genetic disease. Annu. Rev. Med. 62, 107-125.
5. Balch, W. E., Morimoto, R. I., Dillin, A., and Kelly, J. W. (2008). Adapting proteostasis for disease intervention. Science 319, 916-919.
6. Barral, J. M., Broadley, S. A., Schaffar, G., and Hartl, F. U. (2004). Roles of molecular chaperones in protein misfolding diseases. Semin. Cell Dev. Biol. 15, 17-29.
7. Baryshev, M., Sargsyan, E., and Mkrtchian, S. (2006). ERp29 is an essential endoplasmic reticulum factor regulating secretion of thy-roglobulin. Biochem. Biophys. Res. Commun. 340, 617-624.
8. Basile, A., Pascale, M., Franceschelli, S., Nieddu, E., Mazzei, M. T., Fossa, P., Turco, M. C., and Mazzei, M. (2012). Matrine modulates HSC70 levels and rescues DeltaF508-CFTR. J. Cell. Physiol. 227, 3317-3323.
9. Bercovich, B., Stancovski, I., Mayer, A., Blumenfeld, N., Laszlo, A., Schwartz, A. L., and Ciechanover, A. (1997). Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chap-erone Hsc70. J. Biol. Chem. 272, 9002-9010.
10. Bertolotti, A., Zhang, Y., Hendershot, L. M., Harding, H. P., and Ron, D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2, 326-332.
11. Bobadilla, J. L., Macek, M. Jr., Fine, J. P., and Farrell, P. M. (2002). Cystic fibrosis: a worldwide analysis of CFTR mutations - correlation with incidence data and application to screening. Hum. Mutat. 19, 575-606.
12. Chang, X. B., Cui, L., Hou, Y. X., Jensen, T. J., Aleksandrov, A. A., Mengos, A., and Riordan, J. R. (1999). Removal of multiple arginine-framed trafficking signals overcomes mispro-cessing of delta F508 CFTR present in most patients with cystic fibrosis. Mol. Cell 4, 137-142.
13. Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O'Riordan, C. R., and Smith, A. E. (1990). Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63, 827-834.
14. Chiang, H. L., Terlecky, S. R., Plant, C. P., and Dice, J. F. (1989). A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246, 382-385.
15. Cho, H. J., Gee, H. Y., Baek, K. H., Ko, S. K., Park, J. M., Lee, H., Kim, N. D., Lee, M. G., and Shin, I. (2011). A small molecule that binds to an ATPase domain of Hsc70 promotes membrane trafficking of mutant cystic fibrosis transmembrane conductance regulator. J. Am. Chem. Soc. 133, 20267-20276.
16. Cholon, D. M., O'Neal, W. K., Randell, S. H., Riordan, J. R., and Gentzsch, M. (2009). Modulation of endo-cytic trafficking and apical stability of CFTR in primary human airway epithelial cultures. Am. J. Physiol. Lung Cell Mol. Physiol. 298, L304-L314.
17. Choo-Kang, L. R., and Zeitlin, P. L. (2001). Induction of HSP70 promotes DeltaF508 CFTR trafficking. Am. J. Physiol. Lung Cell Mol. Physiol. 281, L58-L68.
18. Clarke, L. L., Gawenis, L. R., Hwang, T. C., Walker, N. M., Gruis, D. B., and Price, E. M. (2004). A domain mimic increases DeltaF508 CFTR trafficking and restores cAMP-stimulated anion secretion in cystic fibrosis epithelia. Am. J. Physiol. Cell Physiol. 287, C192-C199.
19. Collins, F. S. (1992). Cystic fibrosis: molecular biology and therapeutic implications. Science 256, 774-779.
20. Cormet-Boyaka, E., Jablonsky, M., Naren, A. P., Jackson, P. L., Muc-cio, D. D., and Kirk, K. L. (2004). Rescuing cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by transcomplementation. Proc. Natl. Acad. Sci. U. S. A. 101, 8221-8226.
21. Cui, L., Aleksandrov, L., Chang, X. B., Hou, Y. X., He, L., Hege-dus, T., Gentzsch, M., Aleksandrov, A., Balch, W E., and Riordan, J. R. (2007). Domain interdependence in the biosynthetic assembly of CFTR. J. Mol. Biol. 365, 981-994.
22. Cuthbert, A. W (2011). New horizons in the treatment of cystic fibrosis. Br. J. Pharmacol. 163, 173-183.
23. Das, S., Smith, T. D., Sarma, J. D., Ritzen-thaler, J. D., Maza, J., Kaplan, B. E., Cunningham, L. A., Suaud, L., Hub-bard, M. J., Rubenstein, R. C., and Koval, M. (2009). ERp29 restricts Connexin43 oligomerization in the endoplasmic reticulum. Mol. Biol. Cell 20, 2593-2604.
24. DeLuca-Flaherty, C., Mckay, D. B., Parham, P., and Hill, B. L. (1990). Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis. Cell 62, 875-887.
25. Demmer, J., Zhou, C., and Hubbard, M. J. (1997). Molecular cloning of ERp29, a novel and widely expressed resident of the endoplasmic reticulum. FEBSLett. 402, 145-150.
26. Denning, G. M., Anderson, M. P., Amara, J. F., Marshall, J., Smith, A. E., and Welsh, M. J. (1992a). Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 358, 761-764.
27. Denning, G. M., Ostedgaard, L. S., and Welsh, M. J. (1992b). Abnormal localization of cystic fibrosis transmembrane conductance regulator in primary cultures of cystic fibrosis airway epithelia. J. Cell Biol. 118, 551-559.
28. Drumm, M. L., Wilkinson, D. J., Smit, L. S., Worrell, R. T., Strong, T. V., Frizzell, R. A., Dawson, D. C., and Collins, F. S. (1991). Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes. Science 254, 1797-1799.
29. Du, K., Sharma, M., and Lukacs, G. L. (2005). The DeltaF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 12, 17-25.
30. Egan, M. E., Pearson, M., Weiner, S. A., Rajendran, V., Rubin, D., Glockner-Pagel, J., Canny, S., Du, K., Lukacs, G. L., and Caplan, M. J. (2004). Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304, 600-602.
31. Ellis, J. (1987). Proteins as molecular chaperones. Nature 328, 378-379.
32. Farinha, C. M., and Amaral, M. D. (2005). Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol. Cell. Biol. 25, 5242-5252.
33. Farinha, C. M., Nogueira, P., Mendes, E, Penque, D., and Amaral, M. D. (2002). The human DnaJ homo-logue (Hdj)-1/heat-shock protein (Hsp) 40 co-chaperone is required for the in vivo stabilization of the cystic fibrosis transmembrane conductance regulator by Hsp70. Biochem. J. 366, 797-806.
34. Fisher, J. T., Zhang, Y., and Engelhardt, J. F. (2011). Comparative biology of cystic fibrosis animal models. Methods Mol. Biol. 742, 311-334.
35. Fribley, A., Zeng, Q., and Wang, C. Y (2004). Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol. Cell. Biol. 24, 9695-9704.
36. Fuller, W., and Cuthbert, A. W (2000). Post-translational disruption of the delta F508 cystic fibrosis transmembrane conductance regulator (CFTR)-molecular chaperone complex with geldanamycin stabilizes delta F508 CFTR in the rabbit retic-ulocyte lysate. J. Biol. Chem. 275, 37462-37468.
37. Gething, M. J., and Sambrook, J. (1992). Protein folding in the cell. Nature 355, 33-45.
38. Goldfarb, S. B., Kashlan, O. B., Watkins, J. N., Suaud, L., Yan, W., Kley-man, T. R., and Rubenstein, R. C. (2006). Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels. Proc. Natl. Acad. Sci. U. S. A. 103, 5817-5822.
39. Harada, K., Okiyoneda, T., Hashimoto, Y., Oyokawa, K., Nakamura, K., Suico, M. A., Shuto, T., and Kai, H. (2007). Curcumin enhances cystic fibrosis transmembrane regulator expression by down-regulating calreticulin. Biochem. Biophys. Res. Commun. 353, 351-356.
40. Harada, K., Okiyoneda, T., Hashimoto, Y., Ueno, K., Nakamura, K., Yamahira, K., Sugahara, T., Shuto, T., Wada, I., Suico, M. A., and Kai, H. (2006). Calreticulin negatively regulates the cell surface expression of cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 281, 12841-12848.
41. Hartl, F. U. (1996). Molecular chap-erones in cellular protein folding. Nature 381, 571-579.
42. Hubbard, M. J., Mangum, J. E., and Mchugh, N. J. (2004). Purification and biochemical characterization of native ERp29 from rat liver. Biochem. J. 383, 589-597.
43. Hutt, D. M., Powers, E. T., and Balch, W. E. (2009). The proteostasis boundary in misfolding diseases of membrane traffic. FEBS Lett. 583, 2639-2646.
44. Jensen, T. J., Loo, M. A., Pind, S., Williams, D. B., Goldberg, A. L., and Riordan, J. R. (1995). Multiple proteolytic systems, including the protea-some, contribute to CFTR processing. Cell 83, 129-135.
45. 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., and Cheng, S. H. (1998). Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am. J. Physiol. 275, C171-C178.
46. Kalin, N., Claass, A., Sommer, M., Puchelle, E., and Tummler, B. (1999). DeltaF508 CFTR protein expression in tissues from patients with cystic fibrosis. J. Clin. Invest. 103, 1379-1389.
47. Keiser, N. W., and Engelhardt, J. F. (2011). New animal models of cystic fibrosis: what are they teaching us? Curr. Opin. Pulm. Med. 17, 478-483.
48. Kerbiriou, M., Le Drevo, M. A., Ferec, C., and Trouve, P. (2007). Coupling cystic fibrosis to endoplasmic reticulum stress: differential role of Grp78 and ATF6. Biochim. Biophys. Acta 1772, 1236-1249.
49. Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., and Tsui, L. C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080.
50. Kleizen, B., Van Vlijmen, T., De Jonge, H. R., and Braakman, I. (2005). Folding of CFTR is predominantly cotrans-lational. Mol. Cell 20, 277-287.
51. Koulov, A. V., Lapointe, P., Lu, B., Razvi, A., Coppinger, J., Dong, M. Q., Mat-teson, J., Laister, R., Arrowsmith, C., Yates, J. R. III, and Balch, W.E. (2010). Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis. Mol. Biol. Cell 21, 871-884.
52. Lee, A. S. (2005). The ERchaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35, 373-381.
53. Lewis, H. A., Wang, C., Zhao, X., Hamuro, Y., Conners, K., Kearins, M. C., Lu, F., Sauder, J. M., Molnar, K. S., Coales, S. J., Maloney, P. C., Gug-gino, W B., Wetmore, D. R., Weber, P. C., and Hunt, J. F. (2010). Structure and dynamics of NBD1 from CFTR characterized using crystallography and hydrogen/deuterium exchange mass spectrometry. J. Mol. Biol. 396, 406-430.
54. Lewis, H. A., Zhao, X., Wang, C., Sauder, J. M., Rooney, I., Noland, B. W., Lorimer, D., Kearins, M. C., Conners, K., Condon, B., Maloney, P. C., Guggino, W. B., Hunt, J. F., and Emtage, S. (2005). Impact of the deltaF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J. Biol. Chem. 280, 1346-1353.
55. Li, C., Ramjeesingh, M., Reyes, E., Jensen, T., Chang, X., Rommens, J. M., and Bear, C. E. (1993). The cystic fibrosis mutation (delta F508) does not influence the chloride channel activity of CFTR. Nat. Genet. 3, 311-316.
56. Liao, W., Li, X., Mancini, M., and Chan, L. (2006). Proteasome inhibition induces differential heat shock protein response but not unfolded protein response in HepG2 cells. J. Cell. Biochem. 99, 1085-1095.
57. Loo, M. A., Jensen, T. J., Cui, L., Hou, Y., Chang, X. B., and Riordan, J. R. (1998). Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBOJ. 17, 6879-6887.
58. Lukacs, G. L., Chang, X. B., Bear, C., Kartner, N., Mohamed, A., Riordan, J. R., and Grinstein, S. (1993). The delta F508 mutation decreases the stability of cystic fibrosis trans-membrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells. J. Biol. Chem. 268, 21592-21598.
59. Matsumura, Y., David, L. L., and Skach, W. R. (2011). Role of Hsc70 binding cycle in CFTR folding and endoplasmic reticulum-associated degradation. Mol. Biol. Cell 22, 2797-2809.
60. Mayer, M. P., and Bukau, B. (2005). Hsp70 chaperones: cellular functions and molecular mechanism. Cell. Mol. Life Sci. 62, 670-684.
61. Meacham, G. C., Lu, Z., King, S., Sorscher, E., Tousson, A., and Cyr, D. M. (1999). The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. EMBO J. 18, 1492-1505.
62. Meacham, G. C., Patterson, C., Zhang, W., Younger, J. M., and Cyr, D. M. (2001). The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3, 100-105.
63. Morgan, J. R., Prasad, K., Jin, S., Augustine, G. J., and Lafer, E. M. (2001). Uncoating of clathrin-coated vesicles in presynaptic terminals: roles for Hsc70 and auxilin. Neuron 32, 289-300.
64. Murata, S., Chiba, T., and Tanaka, K. (2003). CHIP: a quality-control E3 ligase collaborating with molecular chaperones. Int. J. Biochem. Cell Biol. 35, 572-578.
65. Nadeau, K., Nadler, S. G., Saulnier, M., Tepper, M. A., and Walsh, C. T. (1994). Quantitation of the interaction of the immunosuppressant deoxyspergualin and analogs with Hsc70 and Hsp90. Biochemistry 33, 2561-2567.
66. Nadler, S. G., Tepper, M. A., Schac-ter, B., and Mazzucco, C. E. (1992). Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. Science 258, 484-486.
67. Nanua, S., Sajjan, U., Keshavjee, S., and Hershenson, M. B. (2006). Absence of typical unfolded protein response in primary cultured cystic fibrosis airway epithelial cells. Biochem. Biophys. Res. Commun. 343, 135-143.
68. Norez, C., Pasetto, M., Dechecchi, M. C., Barison, E., Anselmi, C., Tamanini, A., Quiri, F., Cattel, L., Rizzotti, P., Dosio, F., Cabrini, G., and Colom-batti, M. (2008). Chemical conjugation of DeltaF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions. Am. J. Physiol. Lung Cell Mol. Physiol. 295, L336-L347.
69. Okiyoneda, T., Barriere, H., Bagdany, M., Rabeh, W M., Du, K., Hohfeld, J., Young, J. C., and Lukacs, G. L. (2010). Peripheral protein quality control removes unfolded CFTR from the plasma membrane. Science 329, 805-810.
70. Okiyoneda, T., Harada, K., Takeya, M., Yamahira, K., Wada, I., Shuto, T., Suico, M. A., Hashimoto, Y., and Kai, H. (2004). Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin overexpres-sion. Mol. Biol. Cell 15, 563-574.
71. Okiyoneda, T., Niibori, A., Harada, K., Kohno, T., Michalak, M., Duszyk, M., Wada, I., Ikawa, M., Shuto, T., Suico, M. A., and Kai, H. (2008). Role of calnexin in the ER quality control and productive folding of CFTR; differential effect of calnexin knockout on wild-type and DeltaF508 CFTR. Biochim. Biophys. Acta 1783, 1585-1594.
72. Owsianik, G., Cao, L., and Nilius, B. (2003). Rescue of functional DeltaF508-CFTR channels by co-expression with truncated CFTR constructs in COS-1 cells. FEBSLett. 554, 173-178.
73. Park, H. S., Jun Do, Y., Han, C. R., Woo, H. J., and Kim, Y H. (2011). Proteasome inhibitor MG132-induced apoptosis via ER stress-mediated apoptotic pathway and its poten-tiation by protein tyrosine kinase p56lck in human Jurkat T cells. Biochem. Pharmacol. 82, 1110-1125.
74. Pasyk, E. A., and Foskett, J. K. (1995). Mutant (delta F508) cystic fibrosis transmembrane conductance regulator Cl- channel is functional when retained in endoplasmic reticulum of mammalian cells. J. Biol. Chem. 270, 12347-12350.
75. Pearl, L. H., and Prodromou, C. (2006). Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu. Rev. Biochem. 75, 271-294.
76. Pind, S., Riordan, J. R., and Williams, D. B. (1994). Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 269, 12784-12788.
77. Powers, E. T., Morimoto, R. I., Dillin, A., Kelly, J. W., and Balch, W E. (2009). Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78, 959-991.
78. Riordan, J. R. (1999). Cystic fibrosis as a disease of misprocessing of the cystic fibrosis transmembrane conductance regulator glycoprotein. Am. J. Hum. Genet. 64, 1499-1504.
79. Riordan, J. R. (2008). CFTR function and prospects for therapy. Annu. Rev. Biochem. 77, 701-726.
80. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzel-czak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., Drumm, M. L., Iannuzzi, M. C., Collin, F. S., and Tsui, L. -C. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073.
81. Rivett, A. J. (1993). Proteasomes: multicatalytic proteinase complexes. Biochem. J. 291(Pt 1), 1-10.
82. Rubenstein, R. C., Egan, M. E., and Zeitlin, P. L. (1997). In vitro phar-macologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. J. Clin. Invest. 100, 2457-2465.
83. Rubenstein, R. C., and Lyons, B. M. (2001). Sodium 4-phenylbutyrate downregulates HSC70 expression by facilitating mRNA degradation. Am. I Physiol. Lung Cell Mol Physiol. 281, L43-L51.
84. Rubenstein, R. C., and Zeitlin, P. L. (1998). A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function. Am. J.Respir. Crit. Care Med. 157 484-490.
85. Rubenstein, R. C., and Zeitlin, P. L. (2000). Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Am. J. Physiol. Cell Physiol. 278, C259-C267.
86. Sargsyan, E., Baryshev, M., Szekely, L., Sharipo, A., and Mkrtchian, S. (2002). Identification of ERp29, an endoplasmic reticulum lumenal protein, as a new member of the thy-roglobulin folding complex. J. Biol. Chem. 277, 17009-17015.
87. Sato, S., Ward, C. L., and Kopito, R. R. (1998). Cotranslational ubiq-uitination of cystic fibrosis trans-membrane conductance regulator in vitro. J. Biol. Chem. 273, 7189-7192.
88. Schroder, H., Langer, T., Hartl, E U., and Bukau, B. (1993). DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J. 12, 4137-4144.
89. Schroder, M., and Kaufman, R. J. (2005). The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739-789.
90. Serohijos, A. W., Hegedus, T., Alek-sandrov, A. A., He, L., Cui, L., Dokholyan, N. V., and Riordan, J. R. (2008). Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function. Proc. Natl. Acad. Sci. U. S. A. 105, 3256-3261.
91. Strickland, E., Qu, B. H., Millen, L., and Thomas, P. J. (1997). The molecular chaperone Hsc70 assists the in vitro folding of the N-terminal nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 272, 25421-25424.
92. Suaud, L., Miller, K., Alvey, L., Yan, W., Robay, A., Kebler, C., Kreindler, J. L., Guttentag, S., Hubbard, M. J., and Rubenstein, R. C. (2011a). ERp29 regulates DeltaF508 and wild-type cystic fibrosis transmembrane conductance regulator (CFTR) trafficking to the plasma membrane in cystic fibrosis (CF) and non-CF epithelial cells. J. Biol. Chem. 286, 21239-21253.
93. Suaud, L., Miller, K., Panichelli, A. E., Randell, R. L., Marando, C. M., and Rubenstein, R. C. (2011b). 4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells. J. Biol. Chem. 286, 45083-45092.
94. Sun, F., Mi, Z., Condliffe, S. B., Bertrand, C. A., Gong, X., Lu, X., Zhang, R., Latoche, J. D., Pilewski, J. M., Robbins, P. D., and Frizzell, R. A. (2008). Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia. FASEB J. 22, 3255-3263.
95. Sun, F., Zhang, R., Gong, X., Geng, X., Drain, P. F., and Frizzell, R. A. (2006). Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR folding mutants. J. Biol. Chem. 281, 36856-36863.
96. Thibodeau, P. H., Brautigam, C. A., Machius, M., and Thomas, P. J. (2005). Side chain and backbone contributions of Phe508 to CFTR folding. Nat. Struct. Mol. Biol. 12, 10-16.
97. Wang, X., Matteson, J., An, Y., Moyer, B., Yoo, J. S., Bannykh, S., Wilson, I. A., Riordan, J. R., and Balch, W E. (2004). COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. J. Cell Biol. 167, 65-74.
98. Wang, X., Venable, J., Lapointe, P., Hutt, D. M., Koulov, A. V., Coppinger, J., Gurkan, C., Kellner, W., Matteson, J., Plutner, H., Riordan, J. R., Kelly, J. W., Yates, J. R. III, and Balch, W. E. (2006). Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127, 803-815.
99. Ward, C. L., and Kopito, R. R. (1994). Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J. Biol. Chem. 269, 25710-25718.
100. Ward, C. L., Omura, S., and Kopito, R. R. (1995). Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83, 121-127.
101. Wegele, H., Muller, L., and Buchner, J. (2004). Hsp70 and Hsp90 - a relay team for protein folding. Rev. Physiol. Biochem. Pharmacol. 151, 1-44.
102. Wendeler, M. W., Nufer, O., and Hauri, H. P. (2007). Improved maturation of CFTR by an ER export signal. FASEB J. 21, 2352-2358.
103. Wiederkehr, T., Bukau, B., and Buchberger, A. (2002). Protein turnover: a CHIP programmed for proteolysis. Curr. Biol. 12, R26-R28.
104. Wright, J. M., Zeitlin, P. L., Cebotaru, L., Guggino, S. E., and Guggino, W. B. (2004). Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol. Genomics 16, 204-211.
105. Yang, Y., Janich, S., Cohn, J. A., and Wilson, J. M. (1993). 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. 90, 9480-9484.
106. Younger, J. M., Chen, L., Ren, H. Y., Rosser, M. F., Turnbull, E. L., Fan, C. Y., Patterson, C., and Cyr, D. M. (2006). Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell 126, 571-582.
107. Zeitlin, P. L., Diener-West, M., Rubenstein, R. C., Boyle, M. P., Lee, C. K., and Brass-Ernst, L. (2002). Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Mol. Ther. 6, 119-126.
108. Zhang, H., Schmidt, B. Z., Sun, F., Condliffe, S. B., Butterworth, M. B., Youker, R. T., Brodsky, J. L., Aridor, M., and Frizzell, R. A. (2006). Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis. J. Biol. Chem. 281, 11312-11321.