Most F508del-CFTR Is Targeted to Degradation at an Early Folding Checkpoint and Independently of Calnexin

REFERENCES

• Alberti, S., K. Bohse, V. Arndt, A. Schmitz, and J. Hohfeld. 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.
   PubMed Web of Science ®Google Scholar
• Ayalon-Soffer, M., M. Shenkman, and G. Z. Lederkremer. 1999. Differential role of mannose and glucose trimming in the ER degradation of asialoglycoprotein receptor subunits. J. Cell Sci. 112:3309–3318.
   PubMedGoogle Scholar
• Bergeron, J. J., M. B. Brenner, D. Y. Thomas, and D. B. Williams. 1994. Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem. Sci. 19:124–128.
   PubMed Web of Science ®Google Scholar
• Cabral, C. M., Y. Liu, K. W. Moremen, and R. N. Sifers. 2002. Organizational diversity among distinct glycoprotein endoplasmic reticulum-associated degradation programs. Mol. Biol. Cell 13:2639–2650.
   PubMed Web of Science ®Google Scholar
• Cabral, C. M., Y. Liu, and R. N. Sifers. 2001. Dissecting glycoprotein quality control in the secretory pathway. Trends Biochem. Sci. 26:619–624.
   PubMedGoogle Scholar
• Collins, F. S. 1992. Cystic fibrosis: molecular biology and therapeutic implications. Science 256:774–779.
   PubMed Web of Science ®Google Scholar
• Demand, J., S. Alberti, C. Patterson, and J. Hohfeld. 2001. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr. Biol. 11:1569–1577.
   PubMed Web of Science ®Google Scholar
• Du, K., M. Sharma, and G. L. Lukacs. 2004. The DeltaF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 12:17–25.
   PubMedGoogle Scholar
• Egan, M. E., M. Pearson, S. A. Weiner, V. Rajendran, D. Rubin, J. Glockner-Pagel, S. Canny, K. Du, G. L. Lukacs, and M. J. Caplan. 2004. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600–602.
   PubMed Web of Science ®Google Scholar
• Ellgaard, L., and A. Helenius. 2003. Quality control in the endoplasmic reticulum. Nat. Rev. Mol. Cell. Biol. 4:181–191.
   PubMed Web of Science ®Google Scholar
• Farinha, C. M., F. Mendes, M. Roxo-Rosa, D. Penque, and M. D. Amaral. 2004. A comparison of 14 antibodies for the biochemical detection of the cystic fibrosis transmembrane conductance regulator protein. Mol. Cell Probes 18:235–242.
   PubMedGoogle Scholar
• Farinha, C. M., P. Nogueira, F. Mendes, D. Penque, and M. D. Amaral. 2002. The human DnaJ homologue (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.
   PubMed Web of Science ®Google Scholar
• Farinha, C. M., D. Penque, M. Roxo-Rosa, G. Lukacs, R. Dormer, M. McPherson, M. Pereira, A. G. Bot, H. Jorna, R. Willemsen, H. Dejonge, G. D. Heda, C. R. Marino, P. Fanen, A. Hinzpeter, J. Lipecka, J. Fritsch, M. Gentzsch, A. Edelman, and M. D. Amaral. 2004. Biochemical methods to assess CFTR expression and membrane localization. J. Cyst. Fibros. 3(Suppl. 2):73–77.
   PubMedGoogle Scholar
• Gelman, M. S., E. S. Kannegaard, and R. R. Kopito. 2002. A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 277:11709–11714.
   PubMedGoogle Scholar
• Gnann, A., J. R. Riordan, and D. H. Wolf. 2004. CFTR degradation depends on the lectins Htm1p/EDEM and the Cdc48 protein complex in yeast. Mol. Biol. Cell 15:4125–4135.
   PubMed Web of Science ®Google Scholar
• Hammond, C., and A. Helenius. 1994. Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. J. Cell Biol. 126:41–52.
   PubMedGoogle Scholar
• Helenius, A., and M. Aebi. 2004. Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem. 73:1019–1049.
   PubMed Web of Science ®Google Scholar
• Hochstenbach, F., V. David, S. Watkins, and M. B. Brenner. 1992. Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly. Proc. Natl. Acad. Sci. USA 89:4734–4738.
   PubMedGoogle Scholar
• Hohfeld, J., D. M. Cyr, and C. Patterson. 2001. From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep. 2:885–890.
   PubMed Web of Science ®Google Scholar
• Huyer, G., W. F. Piluek, Z. Fansler, S. G. Kreft, M. Hochstrasser, J. L. Brodsky, and S. Michaelis. 2004. Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein. J. Biol. Chem. 279:38369–38378.
   PubMed Web of Science ®Google Scholar
• Jakob, C. A., D. Bodmer, U. Spirig, P. Battig, A. Marcil, D. Dignard, J. J. Bergeron, D. Y. Thomas, and M. Aebi. 2001. Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast. EMBO Rep. 2:423–430.
   PubMed Web of Science ®Google Scholar
• Jensen, T. J., M. A. Loo, S. Pind, D. B. Williams, A. L. Goldberg, and J. R. Riordan. 1995. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83:129–135.
   PubMed Web of Science ®Google Scholar
• Kartner, N., O. Augustinas, T. J. Jensen, A. L. Naismith, and J. R. Riordan. 1992. Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland. Nat. Genet. 1:321–327.
   PubMed Web of Science ®Google Scholar
• Lenk, U., H. Yu, J. Walter, M. S. Gelman, E. Hartmann, R. R. Kopito, and T. Sommer. 2002. A role for mammalian Ubc6 homologues in ER-associated protein degradation. J. Cell Sci. 115:3007–3014.
   PubMed Web of Science ®Google Scholar
• Lewis, H. A., S. G. Buchanan, S. K. Burley, K. Conners, M. Dickey, M. Dorwart, R. Fowler, X. Gao, W. B. Guggino, W. A. Hendrickson, J. F. Hunt, M. C. Kearins, D. Lorimer, P. C. Maloney, K. W. Post, K. R. Rajashankar, M. E. Rutter, J. M. Sauder, S. Shriver, P. H. Thibodeau, P. J. Thomas, M. Zhang, X. Zhao, and S. Emtage. 2004. Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. EMBO J. 23:282–293.
   PubMed Web of Science ®Google Scholar
• Loo, M. A., T. J. Jensen, L. Cui, Y. Hou, X. B. Chang, and J. R. Riordan. 1998. Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J. 17:6879–6887.
   PubMed Web of Science ®Google Scholar
• Mancini, R., M. Aebi, and A. Helenius. 2003. Multiple endoplasmic reticulum-associated pathways degrade mutant yeast carboxypeptidase Y in mammalian cells. J. Biol. Chem. 278:46895–46905.
   PubMedGoogle Scholar
• Marcus, N. Y., and D. H. Perlmutter. 2000. Glucosidase and mannosidase inhibitors mediate increased secretion of mutant alpha1 antitrypsin Z. J. Biol. Chem. 275:1987–1992.
   PubMed Web of Science ®Google Scholar
• McClellan, A. J., and J. Frydman. 2001. Molecular chaperones and the art of recognizing a lost cause. Nat. Cell Biol. 3:E51–E53.
   PubMed Web of Science ®Google Scholar
• Meacham, G. C., Z. Lu, S. King, E. Sorscher, A. Tousson, and D. M. Cyr. 1999. The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. EMBO J. 18:1492–1505.
   PubMed Web of Science ®Google Scholar
• Meacham, G. C., C. Patterson, W. Zhang, J. M. Younger, and D. M. Cyr. 2001. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3:100–105.
   PubMed Web of Science ®Google Scholar
• Molinari, M., V. Calanca, C. Galli, P. Lucca, and P. Paganetti. 2003. Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle. Science 299:1397–1400.
   PubMed Web of Science ®Google Scholar
• Morimoto, R. I. 1998. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 12:3788–3796.
   PubMed Web of Science ®Google Scholar
• Morris, A. P., S. A. Cunningham, D. J. Benos, and R. A. Frizzell. 1993. Glycosylation status of endogenous CFTR does not affect cAMP-stimulated Cl secretion in epithelial cells. Am. J. Physiol. 265:C688–C694.
   PubMedGoogle Scholar
• Oda, Y., N. Hosokawa, I. Wada, and K. Nagata. 2003. EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin. Science 299:1394–1397.
   PubMed Web of Science ®Google Scholar
• Okiyoneda, T., K. Harada, M. Takeya, K. Yamahira, I. Wada, T. Shuto, M. A. Suico, Y. Hashimoto, and H. Kai. 2004. Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin overexpression. Mol. Biol. Cell 15:563–574.
   PubMed Web of Science ®Google Scholar
• Parodi, A. J. 2000. Protein glucosylation and its role in protein folding. Annu. Rev. Biochem. 69:69–93.
   PubMed Web of Science ®Google Scholar
• Peterson, J. R., A. Ora, P. N. Van, and A. Helenius. 1995. Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins. Mol. Biol. Cell. 6:1173–1184.
   PubMedGoogle Scholar
• Pind, S., J. R. Riordan, and D. B. Williams. 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.
   PubMed Web of Science ®Google Scholar
• Qu, B. H., and P. J. Thomas. 1996. Alteration of the cystic fibrosis transmembrane conductance regulator folding pathway. J. Biol. Chem. 271:7261–7264.
   PubMedGoogle Scholar
• Seibert, F. S., Y. Jia, C. J. Mathews, J. W. Hanrahan, J. R. Riordan, T. W. Loo, and D. M. Clarke. 1997. Disease-associated mutations in cytoplasmic loops 1 and 2 of cystic fibrosis transmembrane conductance regulator impede processing or opening of the channel. Biochemistry 36:11966–11974.
   PubMedGoogle Scholar
• Sharma, M., F. Pampinella, C. Nemes, M. Benharouga, J. So, K. Du, K. G. Bache, B. Papsin, N. Zerangue, H. Stenmark, and G. L. Lukacs. 2004. Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes. J. Cell Biol. 164:923–933.
   PubMed Web of Science ®Google Scholar
• Strickland, E., B. H. Qu, L. Millen, and P. J. Thomas. 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.
   PubMedGoogle Scholar
• Svedine, S., T. Wang, R. Halaban, and D. N. Hebert. 2004. Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase. J. Cell Sci. 117:2937–2949.
   PubMedGoogle Scholar
• Thibodeau, P. H., C. A. Brautigam, M. Machius, and P. J. Thomas. 2005. Side chain and backbone contributions of Phe508 to CFTR folding. Nat. Struct. Mol. Biol. 12:10–16.
   PubMed Web of Science ®Google Scholar
• Tokunaga, F., C. Brostrom, T. Koide, and P. Arvan. 2000. Endoplasmic reticulum (ER)-associated degradation of misfolded N-linked glycoproteins is suppressed upon inhibition of ER mannosidase I. J. Biol. Chem. 275:40757–40764.
   PubMedGoogle Scholar
• Tsai, B., Y. Ye, and T. A. Rapoport. 2002. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell Biol. 3:246–255.
   PubMed Web of Science ®Google Scholar
• Urban, S., and M. Freeman. 2003. Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Mol. Cell 11:1425–1434.
   PubMed Web of Science ®Google Scholar
• Varga, K., A. Jurkuvenaite, J. Wakefield, J. S. Hong, J. S. Guimbellot, C. J. Venglarik, A. Niraj, M. Mazur, E. J. Sorscher, J. F. Collawn, and Z. Bebok. 2004. Efficient intracellular processing of the endogenous cystic fibrosis transmembrane conductance regulator in epithelial cell lines. J. Biol. Chem. 279:22578–22584.
   PubMedGoogle Scholar
• Vashist, S., and D. T. Ng. 2004. Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J. Cell Biol. 165:41–52.
   PubMed Web of Science ®Google Scholar
• Wang, J., and A. L. White. 2000. Role of calnexin, calreticulin, and endoplasmic reticulum mannosidase I in apolipoprotein(a) intracellular targeting. Biochemistry 39:8993–9000.
   PubMedGoogle Scholar
• Wang, Y., and M. J. Androlewicz. 2000. Oligosaccharide trimming plays a role in the endoplasmic reticulum-associated degradation of tyrosinase. Biochem. Biophys. Res. Commun. 271:22–27.
   PubMedGoogle Scholar
• Ward, C. L., and R. R. Kopito. 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.
   PubMed Web of Science ®Google Scholar
• Ward, C. L., S. Omura, and R. R. Kopito. 1995. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83:121–127.
   PubMed Web of Science ®Google Scholar
• Wu, B. J., H. C. Hurst, N. C. Jones, and R. I. Morimoto. 1986. The E1A 13S product of adenovirus 5 activates transcription of the cellular human HSP70 gene. Mol. Cell. Biol. 6:2994–2999.
   PubMedGoogle Scholar
• Yang, Y., S. Janich, J. A. Cohn, and J. M. Wilson. 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. USA 90:9480–9484.
   PubMed Web of Science ®Google Scholar
• Younger, J. M., H. Y. Ren, L. Chen, C. Y. Fan, A. Fields, C. Patterson, and D. M. Cyr. 2004. A foldable CFTR{Delta}F508 biogenic intermediate accumulates upon inhibition of the Hsc70-CHIP E3 ubiquitin ligase. J. Cell Biol. 167:1075–1085.
   PubMedGoogle Scholar
• Zhang, F., N. Kartner, and G. L. Lukacs. 1998. Limited proteolysis as a probe for arrested conformational maturation of delta F508 CFTR. Nat. Struct. Biol. 5:180–183.
   PubMedGoogle Scholar
• Zhang, H., K. W. Peters, F. Sun, C. R. Marino, J. Lang, R. D. Burgoyne, and R. A. Frizzell. 2002. Cysteine string protein interacts with and modulates the maturation of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 277:28948–28958.
   PubMedGoogle Scholar
• Zhang, Y., G. Nijbroek, M. L. Sullivan, A. A. McCracken, S. C. Watkins, S. Michaelis, and J. L. Brodsky. 2001. Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol. Biol. Cell 12:1303–1314.
   PubMed Web of Science ®Google Scholar