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The Role of p97/Cdc48p in Endoplasmic Reticulum-Associated Degradation: From the Immune System to Yeast

  • Chapter
Dislocation and Degradation of Proteins from the Endoplasmic Reticulum

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 300))

Abstract

Quality control mechanisms in the endoplasmic reticulum prevent deployment of aberrant or unwanted proteins to distal destinations and target them to degradation by a process known as endoplasmic reticulum-associated degradation, or ERAD. Attempts to characterize ERAD by identifying a specific component have revealed that the most general characteristic of ERAD is that the protein substrates are initially translocated to the ER and eventually eliminated in the cytosol by the ubiquitin-proteasome pathway. Hence, dislocation from the ER back to the cytosol is a hallmark in ERAD and p97/Cdc48p, a cytosolic AAA-ATPase that is essential for ERAD, appears to provide the driving force for this process. Moreover, unlike many ERAD components that participate in degradation of either lumenal or membrane substrates, p97/Cdc48p has a more general role in that it is required for ERAD of both types of substrates. Although p97/Cdc48p is not dedicated exclusively to ERAD, its ability to physically associate with ERAD substrates, with VIMP and with the E3 gp78 suggest that the p97/Cdc48Ufd1/Npl4 complex acts as a coordinator that maintains coupling between the different steps in ERAD.

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References

  • Alberti S, Bohse K, Arndt V, Schmitz A, 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

    Article  CAS  PubMed  Google Scholar 

  • Amitay R, Bar-Nun S, Haimovich J, Rabinovich E, Shachar I (1991) Post-translational regulation of IgM expression in B lymphocytes. J Biol Chem 266:12568–12573

    CAS  PubMed  Google Scholar 

  • Amitay R, Shachar I, Rabinovich E, Haimovich J, Bar-Nun S (1992) Degradation of secretory IgM in B lymphocytes occurs in a post-endoplasmic reticulum compartment and is mediated by a cysteine protease. J Biol Chem 267:20694–20700

    CAS  PubMed  Google Scholar 

  • Bays NW, Gardner RG, Seelig LP, Joazeiro CA, Hampton RY (2001a) Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat Cell Biol 3:24–29

    CAS  PubMed  Google Scholar 

  • Bays NW, Hampton RY (2002) Cdc48-ufd1-npl4: stuck in the middle with ub. Curr Biol 12:R366–R371

    Article  CAS  PubMed  Google Scholar 

  • Bays NW, Wilhovsky SK, Goradia A, Hodgkiss-Harlow K, Hampton RY (2001b) HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins. Mol Biol Cell 12:4114–4128

    CAS  PubMed  Google Scholar 

  • Biederer T, Volkwein C, Sommer T (1996) Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin-proteasome pathway. EMBO J 15:2069–2076

    CAS  PubMed  Google Scholar 

  • Biederer T, Volkwein C, Sommer T (1997) Role of Cue1p in ubiquitination and degradation at the ER surface [see comments]. Science 278:1806–1809

    Article  CAS  PubMed  Google Scholar 

  • Bogyo M, McMaster JS, Gaczynska M, Tortorella D, Goldberg AL, Ploegh H (1997) Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad. Sci U S A 94:6629–6634

    Article  CAS  PubMed  Google Scholar 

  • Bonifacino JS, Weissman AM (1998) Ubiquitin and the control of protein fate in the secretory and endocytic pathways. Annu Rev Cell Dev Biol 14:19–57

    Article  CAS  PubMed  Google Scholar 

  • Bordallo J, Plemper RK, Finger A, Wolf DH (1998) Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol Biol Cell 9:209–222

    CAS  PubMed  Google Scholar 

  • Braun S, Matuschewski K, Rape M, Thoms S, Jentsch S (2002) Role of the ubiquitinselective CDC48(UFD1/NPL4) chaperone (segregase) in ERADofOLE1 and other substrates. EMBO J 21:615–621

    Article  CAS  PubMed  Google Scholar 

  • Brodsky JL, McCracken AA (1999) ER protein quality control and proteasomemediated protein degradation. Semin Cell Dev Biol 10:507–513

    CAS  PubMed  Google Scholar 

  • Brodsky JL, Werner ED, Dubas ME, Goeckeler JL, Kruse KB, McCracken AA (1999) The requirement for molecular chaperones during endoplasmic reticulum-associated protein degradation demonstrates that protein export and import are mechanistically distinct. J Biol Chem 274:3453–3460

    Article  CAS  PubMed  Google Scholar 

  • Brooks P, Fuertes G, Murray RZ, Bose S, Knecht E, Rechsteiner MC, Hendil KB, Tanaka K, Dyson J, Rivett J (2000) Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem J 346:155–161

    Article  CAS  PubMed  Google Scholar 

  • Caldwell SR, Hill KJ, Cooper AA (2001) Degradation of endoplasmic reticulum (ER) quality control substrates requires transport between the ER and Golgi. J Biol Chem 276:23296–23303

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Bonifacino JS, Yuan YC, Klausner RD (1988) Selective degradation of T-cell antigen receptor chains retained in a pre-Golgi compartment. J Cell Biol 107:2149–2161

    CAS  PubMed  Google Scholar 

  • Cyr DM, Hohfeld J, Patterson C (2002) Protein quality control: U-box-containing E3 ubiquitin ligases join the fold. Trends Biochem Sci 27:368–375

    Article  CAS  PubMed  Google Scholar 

  • Dai RM, Chen E, Longo DL, Gorbea CM, Li CC (1998) Involvement of valosin-containing protein, an ATPase co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha. J Biol Chem 273:3562–3573

    CAS  PubMed  Google Scholar 

  • Dai RM, Li CC (2001) Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol 3:740–744

    Article  CAS  PubMed  Google Scholar 

  • Elkabetz Y, Kerem A, Tencer L, Winitz D, Kopito RR, Bar-Nun S (2003) Immunoglobulin light chains dictate vesicular transport-dependent and-independent routes for IgM degradation by the ubiquitin-proteasome pathway. J Biol Chem 278:18922–18929

    Article  CAS  PubMed  Google Scholar 

  • Elkabetz Y, Shapira I, Rabinovich E, Bar-Nun S (2004) Distinct steps in dislocation of luminal endoplasmic reticulum-associated degradation substrates: roles of endoplasmic reticulum-bound p97/Cdc48p and proteasome. J Biol Chem 279:3980–3989

    CAS  PubMed  Google Scholar 

  • Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181–191

    Article  CAS  PubMed  Google Scholar 

  • Enenkel C, Lehmann A, Kloetzel PM (1998) Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast. EMBO J 17:6144–6154

    Article  CAS  PubMed  Google Scholar 

  • Fang S, Ferrone M, Yang C, Jensen JP, Tiwari S, Weissman AM (2001) The tumor autocrinemotility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proc Natl Acad Sci U S A 98:14422–14427

    CAS  PubMed  Google Scholar 

  • Flierman D, Ye Y, Dai M, Chau V, Rapoport TA (2003) Polyubiquitin serves as a recognition signal, rather than a ratcheting molecule, during retrotranslocation of proteins across the endoplasmic reticulum membrane. J Biol Chem 278:34774–34782

    Article  CAS  PubMed  Google Scholar 

  • Friedlander R, Jarosch E, Urban J, Volkwein C, Sommer T (2000) A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat Cell Biol 2:379–384

    CAS  PubMed  Google Scholar 

  • Galan JM, Cantegrit B, Garnier C, Namy O, Haguenauer-Tsapis R (1998) ‘ER degradation’ of amutant yeast plasma membrane protein by the ubiquitin-proteasome pathway. FASEB J 12:315–323

    CAS  PubMed  Google Scholar 

  • Gardner RG, Hampton RY (1999) A ‘distributed degron’ allows regulated entry into the ER degradation pathway. EMBO J 18:5994–6004

    CAS  PubMed  Google Scholar 

  • Ghislain M, Dohmen RJ, Levy F, Varshavsky A (1996) Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO J 15:4884–4899

    CAS  PubMed  Google Scholar 

  • Gillece P, Luz JM, Lennarz WJ, de la Cruz FJ, Romisch K (1999) Export of a cysteinefree misfolded secretory protein from the endoplasmic reticulumfor degradation requires interaction with protein disulfide isomerase. J Cell Biol 147:1443–1456

    Article  CAS  PubMed  Google Scholar 

  • Gitan RS, Eide DJ (2000) Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter. Biochem J 346:329–336

    Article  CAS  PubMed  Google Scholar 

  • Gnann A, Riordan JR, Wolf DH (2004) Cystic fibrosis transmembrane conductance regulator degradation dependsonthe lectins Htm1p/EDEM and the Cdc48 protein complex in yeast. Mol Biol Cell 15:4125–4135

    Article  CAS  PubMed  Google Scholar 

  • Gusarova V, Caplan AJ, Brodsky JL, Fisher EA (2001) Apoprotein B degradation is promoted by themolecular chaperones hsp90 and hsp70. J Biol Chem 276:24891–24900

    Article  CAS  PubMed  Google Scholar 

  • Hammond C, Helenius A (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

    Article  CAS  PubMed  Google Scholar 

  • Hampton RY, Bhakta H (1997) Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Proc Natl Acad Sci U S A 94:12944–12948

    Article  CAS  PubMed  Google Scholar 

  • Hampton RY, Gardner RG, Rine J (1996) Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell 7:2029–2044

    CAS  PubMed  Google Scholar 

  • Haynes CM, Caldwell S, Cooper AA (2002) An HRD/DER-independent ER quality control mechanism involves Rsp5p-dependent ubiquitination and ER-Golgi transport. J Cell Biol 158:91–101

    Article  CAS  PubMed  Google Scholar 

  • Hebert DN, Simons JF, Peterson JR, Helenius A (1995) Calnexin, calreticulin, and Bip/Kar2p in protein folding. Cold Spring Harb Symp Quant Biol 60:405–415

    CAS  PubMed  Google Scholar 

  • Heinemeyer W, Fischer M, Krimmer T, Stachon U, Wolf DH (1997) The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem 272:25200–25209

    Article  CAS  PubMed  Google Scholar 

  • Heinemeyer W, Kleinschmidt JA, Saidowsky J, Escher C, Wolf DH (1991) Proteinase yscE, the yeast proteasome/multicatalytic-multifunctional proteinase: mutants unravel its function in stress induced proteolysis and uncover its necessity for cell survival. EMBO J 10:555–562

    CAS  PubMed  Google Scholar 

  • Hendershot LM (1990) Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition. J Cell Biol 111:829–837

    Article  CAS  PubMed  Google Scholar 

  • Hill K, Cooper AA (2000) Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system. EMBO J 19:550–561

    CAS  PubMed  Google Scholar 

  • Hiller MM, Finger A, Schweiger M, Wolf DH (1996) ER degradation of a misfolded luminal protein by a cytosolic ubiquitin-proteasome pathway. Science 273:1725–1728

    CAS  PubMed  Google Scholar 

  • Hirsch C, Ploegh HL (2000) Intracellular targeting of the proteasome. Trends Cell Biol 10:268–272

    Article  CAS  PubMed  Google Scholar 

  • Hori H, Nembai T, Miyata Y, Hayashi T, Ueno K, Koide T (1999) Isolation and characterization of two 20S proteasomes from the endoplasmic reticulum of rat liver microsomes. J Biochem (Tokyo) 126:722–730

    CAS  PubMed  Google Scholar 

  • Huyer G, Piluek WF, Fansler Z, Kreft SG, Hochstrasser M, Brodsky JL, Michaelis S (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

    Article  CAS  PubMed  Google Scholar 

  • Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R (2002) CHIP is associated with Parkin, a gene responsible for familial Parkinson’s disease, and enhances its ubiquitin ligase activity. Mol Cell 10:55–67

    Article  CAS  PubMed  Google Scholar 

  • Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105:891–902

    Article  CAS  PubMed  Google Scholar 

  • Jarosch E, Taxis C, Volkwein C, Bordallo J, Finley D, Wolf DH, Sommer T (2002) Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48. Nat Cell Biol 4:134–139

    Article  CAS  PubMed  Google Scholar 

  • Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR (1995) Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83:129–135

    Article  CAS  PubMed  Google Scholar 

  • Kaneko M, Ishiguro M, Niinuma Y, Uesugi M, Nomura Y (2002)HumanHRD1 protects against ER stress-induced apoptosis through ER-associated degradation. FEBS Lett 532:147–152

    Article  CAS  PubMed  Google Scholar 

  • Kikkert M, Doolman R, Dai M, Avner R, Hassink G, van Voorden S, Thanedar S, Roitelman J, Chau V, Wiertz E (2004) Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem 279:3525–3534

    CAS  PubMed  Google Scholar 

  • Klausner RD, Sitia R (1990) Protein degradation in the endoplasmic reticulum. Cell 62:611–614

    Article  CAS  PubMed  Google Scholar 

  • Klausner RD, Lippincott-Schwartz J, Bonifacino JS (1990) The T cell antigen receptor: insights into organelle biology. Annu Rev Cell Biol 6:403–431

    Article  CAS  PubMed  Google Scholar 

  • Knop M, Finger A, Braun T, Hellmuth K, Wolf DH (1996) Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. EMBO J 15:753–763

    CAS  PubMed  Google Scholar 

  • Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S (1999) A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96:635–644

    Article  CAS  PubMed  Google Scholar 

  • Kopito RR (1997) ER quality control: the cytoplasmic connection. Cell 88:427–430

    Article  CAS  PubMed  Google Scholar 

  • Lavoie C, Chevet E, Roy L, Tonks NK, Fazel A, Posner BI, Paiement J, Bergeron JJ (2000) Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro. Proc Natl Acad Sci U S A 97:13637–13642

    Article  CAS  PubMed  Google Scholar 

  • Lee YK, Brewer JW, Hellman R, Hendershot LM (1999) BiP and immunoglobulin light chain cooperate to control the folding of heavy chain and ensure the fidelity of immunoglobulin assembly. Mol Biol Cell 10:2209–2219

    CAS  PubMed  Google Scholar 

  • Lilley BN, Ploegh HL (2004)Amembrane protein required for dislocation of misfolded proteins from the ER. Nature 429:834–840

    Article  CAS  PubMed  Google Scholar 

  • Loayza D, Tam A, Schmidt WK, Michaelis S (1998) Ste6pmutants defective in exit from the endoplasmic reticulum (ER) reveal aspects of an ER quality control pathway in Saccharomyces cerevisiae. Mol Biol Cell 9:2767–2784

    CAS  PubMed  Google Scholar 

  • Mancini R, Fagioli C, Fra AM, Maggioni C, Sitia R (2000) Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events. FASEB J 14:769–778

    CAS  PubMed  Google Scholar 

  • Matlack KE, Misselwitz B, Plath K, Rapoport TA (1999) BiP acts as a molecular ratchet during posttranslational transport of prepro-alpha factor across the ER membrane. Cell 97:553–564

    Article  CAS  PubMed  Google Scholar 

  • Mayer TU, Braun T, Jentsch S (1998) Role of the proteasome in membrane extraction of a short-lived ER transmembrane protein. EMBO J 17:3251–3257

    Article  CAS  PubMed  Google Scholar 

  • McCracken AA, Brodsky JL (1996) Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP. J Cell Biol 132:291–298

    Article  CAS  PubMed  Google Scholar 

  • Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol 3:100–105

    CAS  PubMed  Google Scholar 

  • Medicherla B, Kostova Z, Schaefer A, Wolf DH (2004) A genomic screen identifies Dsk2p and Rad23p as essential components of ER-associated degradation. EMBO Rep 5:692–697

    Article  CAS  PubMed  Google Scholar 

  • Meerovitch K, Wing S, Goltzman D (1998) Proparathyroid hormone-related protein is associated with the chaperone protein BiP and undergoes proteasome-mediated degradation. J Biol Chem 273:21025–21030

    Article  CAS  PubMed  Google Scholar 

  • Meusser B, Sommer T (2004) Vpu-mediated degradation of CD4 reconstituted in yeast reveals mechanistic differences to cellular ER-associated protein degradation. Mol Cell 14:247–258

    Article  CAS  PubMed  Google Scholar 

  • Meyer HH, Wang Y, Warren G (2002) Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4. EMBO J 21:5645–5652

    CAS  PubMed  Google Scholar 

  • Nadav E, Shmueli A, Barr H, Gonen H, Ciechanover A, Reiss Y (2003) A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1. Biochem Biophys Res Commun 303:91–97

    Article  CAS  PubMed  Google Scholar 

  • Nishikawa S, Fewell SW, Kato Y, Brodsky JL, Endo T (2001) Molecular chaperones in the yeast endoplasmic reticulum maintain the solubility of proteins for retro-translocation and degradation. J Cell Biol 153:1061–1070

    Article  CAS  PubMed  Google Scholar 

  • Pilon M, Schekman R, Romisch K (1997) Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation. EMBO J 16:4540–4548

    Article  CAS  PubMed  Google Scholar 

  • Plemper RK, Bohmler S, Bordallo J, Sommer T, Wolf DH (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature 388:891–895

    Article  CAS  PubMed  Google Scholar 

  • Plemper RK, Egner R, Kuchler K, Wolf DH (1998) Endoplasmic reticulum degradation of a mutated ATP-binding cassette transporter Pdr5proceeds in a concerted action of Sec61 and the proteasome. J Biol Chem 273:32848–32856

    Article  CAS  PubMed  Google Scholar 

  • Rabinovich E, Bar-Nun S, Amitay R, Shachar I, Gur B, Taya M, Haimovich J (1993) Different assembly species of IgM are directed to distinct degradation sites along the secretory pathway. J Biol Chem 268:24145–24148

    CAS  PubMed  Google Scholar 

  • Rabinovich E, Kerem A, Frohlich KU, Diamant N, Bar-Nun S (2002) AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation. Mol Cell Biol 22:626–634

    Article  CAS  PubMed  Google Scholar 

  • Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S (2001) Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 107:667–677

    Article  CAS  PubMed  Google Scholar 

  • Riezman H (1997) The ins and outs of protein translocation. Science 278:1728–1729

    Article  CAS  PubMed  Google Scholar 

  • Rivett AJ (1998) Intracellular distribution of proteasomes. Curr Opin Immunol 10:110–114

    Article  CAS  PubMed  Google Scholar 

  • Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (1994) Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771

    Article  CAS  PubMed  Google Scholar 

  • Romisch K (1999) Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane. J Cell Sci 112:4185–4191

    CAS  PubMed  Google Scholar 

  • Rouiller I, Butel VM, Latterich M, Milligan RA, Wilson-Kubalek EM (2000) A major conformational change in p97 AAA ATPase upon ATP binding. Mol Cell 6:1485–1490

    Article  CAS  PubMed  Google Scholar 

  • Rubin DM, Glickman MH, Larsen CN, Dhruvakumar S, Finley D (1998) Active site mutants in the six regulatory particle ATPases reveal multiple roles for ATP in the proteasome. EMBO J 17:4909–4919

    Article  CAS  PubMed  Google Scholar 

  • Shachar I, Amitay R, Rabinovich E, Haimovich J, Bar-Nun S (1992) Polymerization of secretory IgM in B lymphocytes is prevented by a preceding targeting to a degradation pathway. J Biol Chem 267:24241–24247

    CAS  PubMed  Google Scholar 

  • Sommer T, Jentsch S (1993) A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 365:176–179

    Article  CAS  PubMed  Google Scholar 

  • Spear ED, Ng DT (2003) Stress tolerance of misfolded carboxypeptidase Y requires maintenance of protein trafficking and degradative pathways. Mol Biol Cell 14:2756–2767

    Article  CAS  PubMed  Google Scholar 

  • Stafford FJ, Bonifacino JS (1991) A permeabilized cell system identifies the endoplasmic reticulum as a site of protein degradation. J Cell Biol 115:1225–1236

    Article  CAS  PubMed  Google Scholar 

  • Swanson R, Locher M, Hochstrasser M (2001) A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation. Genes Dev 15:2660–2674

    Article  CAS  PubMed  Google Scholar 

  • Taxis C, Hitt R, Park SH, Deak PM, Kostova Z, Wolf DH (2003) Use of modular substrates demonstrates mechanistic diversity and reveals differences in chaperone requirement of ERAD. J Biol Chem 278:35903–35913

    Article  CAS  PubMed  Google Scholar 

  • Tiwari S, Weissman AM (2001) Endoplasmic reticulum (ER)-associated degradation of T cell receptor subunits. Involvement of ER-associated ubiquitin-conjugating enzymes (E2s). J Biol Chem 276:16193–16200

    Article  CAS  PubMed  Google Scholar 

  • Tsai B, Rodighiero C, Lencer WI, Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937–948

    Article  CAS  PubMed  Google Scholar 

  • Vashist S, Kim W, Belden WJ, Spear ED, Barlowe C, Ng DT (2001) Distinct retrieval and retention mechanisms are required for the quality control of endoplasmic reticulum protein folding. J Cell Biol 155:355–368

    Article  CAS  PubMed  Google Scholar 

  • Vashist S, Ng DTW (2004) Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J Cell Biol 165:41–52

    Article  CAS  PubMed  Google Scholar 

  • Verma R, Chen S, Feldman R, Schieltz D, Yates J, Dohmen J, Deshaies RJ (2000) Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol Biol Cell 11:3425–3439

    CAS  PubMed  Google Scholar 

  • Vogel JP, Misra LM, Rose MD (1990) Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast. J Cell Biol 110:1885–1895

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Alam SL, Meyer HH, Payne M, Stemmler TL, Davis DR, Sundquist WI (2003) Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4. J Biol Chem 278:20225–20234

    CAS  PubMed  Google Scholar 

  • Wang Q, Chang A (2003) Substrate recognition in ER-associated degradation mediated by Eps1, a member of the protein disulfide isomerase family. EMBO J 22:3792–3802

    CAS  PubMed  Google Scholar 

  • Ward CL, Omura S, Kopito RR (1995) Degradation of CFTR by the ubiquitinproteasome pathway. Cell 83:121–127

    Article  CAS  PubMed  Google Scholar 

  • Wiertz EJHJ, Tortorella D, Bogyo M, Yu J, Mothes W, Jones TR, Rapoport TA, Ploegh HL (1996) Sec61-mediated transfer of membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384:432–438

    Article  CAS  PubMed  Google Scholar 

  • Wilhovsky S, Gardner R, Hampton R (2000) HRD gene dependence of endoplasmic reticulum-associated degradation [In Process Citation]. Mol Biol Cell 11:1697–1708

    CAS  PubMed  Google Scholar 

  • Wilkinson BM, Tyson JR, Reid PJ, Stirling CJ (2000) Distinct domains within yeast Sec61p involved in post-translational translocation and protein dislocation. J Biol Chem 275:521–529

    CAS  PubMed  Google Scholar 

  • Winitz D, Shachar I, Elkabetz Y, Amitay R, Samuelov M, Bar-Nun S (1996) Degradation of distinct assembly forms of immunoglobulin M occurs in multiple sites in permeabilized B cells. J Biol Chem 271:27645–27651

    CAS  PubMed  Google Scholar 

  • Ye Y, Meyer HH, Rapoport TA (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 414:652–656

    Article  CAS  PubMed  Google Scholar 

  • Ye Y, Meyer HH, Rapoport TA (2003) Function of the p97-Ufd1-Npl4 complex in retro-translocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains. J Cell Biol 162:71–84

    Article  CAS  PubMed  Google Scholar 

  • Ye Y, Shibata Y, Yun C, Ron D, Rapoport TA (2004) A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429:841–847

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K, Tai T (2002) E3 ubiquitin ligase that recognizes sugar chains. Nature 418:438–442

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Tokunaga F, Chiba T, Iwai K, Tanaka K, Tai T (2003) Fbs2 is a new member of the E3 ubiquitin ligase family that recognizes sugar chains. J Biol Chem 278:43877–43884

    CAS  PubMed  Google Scholar 

  • Zhang Y, Nijbroek G, Sullivan ML, McCracken AA, Watkins SC, Michaelis S, Brodsky JL (2001) Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol Biol Cell 12:1303–1314

    CAS  PubMed  Google Scholar 

  • Zhong X, Shen Y, Ballar P, Apostolou A, Agami R, Fang S (2004) AAA ATPase p97/VCP interacts with gp78: a ubiquitin ligase for ER-associated degradation. J Biol Chem 279:45676–45684

    CAS  PubMed  Google Scholar 

  • Zhou M, Schekman R (1999) The engagement of Sec61p in the ER dislocation process. Mol Cell 4:925–934

    CAS  PubMed  Google Scholar 

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  1. Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    S. Bar-Nun

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  1. Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

    Emmanuel Wiertz Ph. D.  & Marjolein Kikkert Ph. D.  & 

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© 2006 Springer-Verlag Berlin Heidelberg

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Bar-Nun, S. (2006). The Role of p97/Cdc48p in Endoplasmic Reticulum-Associated Degradation: From the Immune System to Yeast. In: Wiertz, E., Kikkert, M. (eds) Dislocation and Degradation of Proteins from the Endoplasmic Reticulum. Current Topics in Microbiology and Immunology, vol 300. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28007-3_5

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