Cleaning up in the endoplasmic reticulum: ubiquitin in charge (original) (raw)

• Brodsky, J.L. & Wojcikiewicz, R.J. Substrate-specific mediators of ER associated degradation (ERAD). Curr. Opin. Cell Biol. 21, 516–521 (2009).
  CAS PubMed PubMed Central Google Scholar
• Hampton, R.Y. ER-associated degradation in protein quality control and cellular regulation. Curr. Opin. Cell Biol. 14, 476–482 (2002).
  CAS PubMed Google Scholar
• Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519–529 (2007).
  CAS PubMed Google Scholar
• Needham, P.G. & Brodsky, J.L. How early studies on secreted and membrane protein quality control gave rise to the ER associated degradation (ERAD) pathway: the early history of ERAD. Biochim. Biophys. Acta 1833, 2447–2457 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lippincott-Schwartz, J., Bonifacino, J.S., Yuan, L.C. & Klausner, R.D. Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins. Cell 54, 209–220 (1988).Refs. 5 and 6 were the first to demonstrate that unassembled endogenous membrane proteins are rapidly degraded after import into the ER, thus defining a new pathway of protein degradation at the ER.
  CAS PubMed Google Scholar
• Bonifacino, J.S., Cosson, P. & Klausner, R.D. Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains. Cell 63, 503–513 (1990).
  CAS PubMed Google Scholar
• Ward, C.L., Omura, S. & Kopito, R.R. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83, 121–127 (1995).Refs. 7, 8, 9, 10, 11, 12 demonstrated that ERAD requires the ubiquitin-proteasome system, thus suggesting that the substrates need to be retrotranslocated into the cytosol before degradation.
  CAS PubMed Google Scholar
• Sommer, T. & Jentsch, S. A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 365, 176–179 (1993).
  CAS PubMed Google Scholar
• Hiller, M.M., Finger, A., Schweiger, M. & Wolf, D.H. ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway. Science 273, 1725–1728 (1996).
  CAS PubMed Google Scholar
• Hampton, R.Y., Gardner, R.G. & Rine, J. 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 (1996).
  CAS PubMed PubMed Central Google Scholar
• Jensen, T.J. et al. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 83, 129–135 (1995).
  CAS PubMed Google Scholar
• Wiertz, E.J. et al. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84, 769–779 (1996).
  CAS PubMed Google Scholar
• Tsai, B., Ye, Y. & Rapoport, T.A. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell Biol. 3, 246–255 (2002).
  CAS PubMed Google Scholar
• Shimizu, Y., Okuda-Shimizu, Y. & Hendershot, L.M. Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids. Mol. Cell 40, 917–926 (2010).
  CAS PubMed PubMed Central Google Scholar
• Wang, X. et al. Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. J. Cell Biol. 177, 613–624 (2007).
  CAS PubMed PubMed Central Google Scholar
• Ishikura, S., Weissman, A.M. & Bonifacino, J.S. Serine residues in the cytosolic tail of the T-cell antigen receptor α-chain mediate ubiquitination and endoplasmic reticulum-associated degradation of the unassembled protein. J. Biol. Chem. 285, 23916–23924 (2010).
  CAS PubMed PubMed Central Google Scholar
• Pickart, C.M. & Fushman, D. Polyubiquitin chains: polymeric protein signals. Curr. Opin. Chem. Biol. 8, 610–616 (2004).
  CAS PubMed Google Scholar
• Li, W. & Ye, Y. Polyubiquitin chains: functions, structures, and mechanisms. Cell. Mol. Life Sci. 65, 2397–2406 (2008).
  CAS PubMed PubMed Central Google Scholar
• Kim, W. et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44, 325–340 (2011).
  CAS PubMed PubMed Central Google Scholar
• van der Veen, A.G. & Ploegh, H.L. Ubiquitin-like proteins. Annu. Rev. Biochem. 81, 323–357 (2012).
  CAS PubMed Google Scholar
• Ahner, A. et al. Small heat shock proteins target mutant cystic fibrosis transmembrane conductance regulator for degradation via a small ubiquitin-like modifier–dependent pathway. Mol. Biol. Cell 24, 74–84 (2013).
  CAS PubMed PubMed Central Google Scholar
• Pickart, C.M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503–533 (2001).
  CAS PubMed Google Scholar
• Bays, N.W., Gardner, R.G., Seelig, L.P., Joazeiro, C.A. & Hampton, R.Y. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat. Cell Biol. 3, 24–29 (2001).Refs. 23 and 24 identified the two major ubiquitin ligases involved in ERAD in budding yeast.
  CAS PubMed Google Scholar
• Swanson, R., Locher, M. & Hochstrasser, M. A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matα2 repressor degradation. Genes Dev. 15, 2660–2674 (2001).
  CAS PubMed PubMed Central Google Scholar
• Stolz, A., Besser, S., Hottmann, H. & Wolf, D.H. Previously unknown role for the ubiquitin ligase Ubr1 in endoplasmic reticulum–associated protein degradation. Proc. Natl. Acad. Sci. USA 110, 15271–15276 (2013).
  CAS PubMed PubMed Central Google Scholar
• Vashist, S. & Ng, D.T. Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J. Cell Biol. 165, 41–52 (2004).Refs. 26 and 27 elucidated different routes by which distinct classes of misfolded ER proteins are retrotranslocated for degradation.
  CAS PubMed PubMed Central Google Scholar
• Carvalho, P., Goder, V. & Rapoport, T.A. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell 126, 361–373 (2006).
  CAS PubMed Google Scholar
• Mehnert, M., Sommer, T. & Jarosch, E. ERAD ubiquitin ligases: multifunctional tools for protein quality control and waste disposal in the endoplasmic reticulum. Bioessays 32, 905–913 (2010).
  CAS PubMed Google Scholar
• Mueller, B., Klemm, E.J., Spooner, E., Claessen, J.H. & Ploegh, H.L. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc. Natl. Acad. Sci. USA 105, 12325–12330 (2008).
  CAS PubMed PubMed Central Google Scholar
• Wang, X. et al. Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates. J. Cell Biol. 187, 655–668 (2009).
  CAS PubMed PubMed Central Google Scholar
• Chen, Z., Du, S. & Fang, S. gp78: a multifaceted ubiquitin ligase that integrates a unique protein degradation pathway from the endoplasmic reticulum. Curr. Protein Pept. Sci. 13, 414–424 (2012).
  CAS PubMed Google Scholar
• Bernasconi, R., Galli, C., Calanca, V., Nakajima, T. & Molinari, M. Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates. J. Cell Biol. 188, 223–235 (2010).
  CAS PubMed PubMed Central Google Scholar
• Christianson, J.C. et al. Defining human ERAD networks through an integrative mapping strategy. Nat. Cell Biol. 14, 93–105 (2012).This paper used a systems-biology approach to construct a complex functional-interaction map of the proteins involved in mammalian ERAD.
  CAS Google Scholar
• Younger, J.M. et al. Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell 126, 571–582 (2006).
  CAS PubMed Google Scholar
• Morito, D. et al. Gp78 cooperates with RMA1 in endoplasmic reticulum–associated degradation of CFTRDeltaF508. Mol. Biol. Cell 19, 1328–1336 (2008).
  CAS PubMed PubMed Central Google Scholar
• Komander, D., Clague, M.J. & Urbe, S. Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 10, 550–563 (2009).
  CAS PubMed Google Scholar
• Ernst, R., Mueller, B., Ploegh, H.L. & Schlieker, C. The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Mol. Cell 36, 28–38 (2009).
  CAS PubMed PubMed Central Google Scholar
• Sowa, M.E., Bennett, E.J., Gygi, S.P. & Harper, J.W. Defining the human deubiquitinating enzyme interaction landscape. Cell 138, 389–403 (2009).
  CAS PubMed PubMed Central Google Scholar
• Wang, Q., Li, L. & Ye, Y. Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3. J. Cell Biol. 174, 963–971 (2006).
  CAS PubMed PubMed Central Google Scholar
• Ernst, R. et al. Enzymatic blockade of the ubiquitin-proteasome pathway. PLoS Biol. 8, e1000605 (2011).
  PubMed Google Scholar
• Bernardi, K.M., Williams, J.M., Inoue, T., Schultz, A. & Tsai, B. A deubiquitinase negatively regulates retro-translocation of non-ubiquitinated substrates. Mol. Biol. Cell 24, 3545–3556 (2013).
  CAS PubMed PubMed Central Google Scholar
• Liu, Y. et al. USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation. Elife 3, e01369 (2014).This paper reported that a machinery protein in ERAD could be subject to regulation by ubiquitination in a proteasome-independent manner.
  PubMed PubMed Central Google Scholar
• Zhang, Z.R., Bonifacino, J.S. & Hegde, R.S. Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER. Cell 154, 609–622 (2013).
  CAS PubMed PubMed Central Google Scholar
• Schubert, U. et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770–774 (2000).
  CAS PubMed Google Scholar
• Ye, Y., Meyer, H.H. & Rapoport, T.A. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 414, 652–656 (2001).Refs. 45, 46, 47, 48 and 54 demonstrated the involvement of the AAA+ ATPase p97/VCP in ERAD. Ref. 45 also used an in vitro retrotranslocation assay to show that p97/VCP is required to move ubiquitinated ERAD substrates from the membranes to the cytosol for degradation by the proteasome.
  CAS PubMed Google Scholar
• Rabinovich, E., Kerem, A., Frohlich, K.U., Diamant, N. & Bar-Nun, S. AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum–associated protein degradation. Mol. Cell. Biol. 22, 626–634 (2002).
  CAS PubMed PubMed Central Google Scholar
• Jarosch, E. et al. Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48. Nat. Cell Biol. 4, 134–139 (2002).
  CAS PubMed Google Scholar
• Bays, N.W., Wilhovsky, S.K., Goradia, A., Hodgkiss-Harlow, K. & Hampton, R.Y. HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins. Mol. Biol. Cell 12, 4114–4128 (2001).
  CAS PubMed PubMed Central Google Scholar
• Ye, Y. Diverse functions with a common regulator: ubiquitin takes command of an AAA ATPase. J. Struct. Biol. 156, 29–40 (2006).
  CAS PubMed Google Scholar
• DeLaBarre, B. & Brunger, A.T. Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains. Nat. Struct. Biol. 10, 856–863 (2003).
  CAS PubMed Google Scholar
• Zhang, X. et al. Structure of the AAA ATPase p97. Mol. Cell 6, 1473–1484 (2000).
  CAS PubMed Google Scholar
• Meyer, H., Bug, M. & Bremer, S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat. Cell Biol. 14, 117–123 (2012).
  CAS PubMed Google Scholar
• Flierman, D., Ye, Y., Dai, M., Chau, V. & Rapoport, T.A. 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 (2003).
  CAS PubMed Google Scholar
• Ye, Y., Meyer, H.H. & Rapoport, T.A. Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains. J. Cell Biol. 162, 71–84 (2003).
  CAS PubMed PubMed Central Google Scholar
• Liu, Y. & Ye, Y. Roles of p97-associated deubiquitinases in protein quality control at the endoplasmic reticulum. Curr. Protein Pept. Sci. 13, 436–446 (2012).
  CAS PubMed PubMed Central Google Scholar
• Rape, M. et al. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 107, 667–677 (2001).
  CAS PubMed Google Scholar
• Garza, R.M., Sato, B.K. & Hampton, R.Y. In vitro analysis of Hrd1p-mediated retrotranslocation of its multispanning membrane substrate 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase. J. Biol. Chem. 284, 14710–14722 (2009).
  CAS PubMed PubMed Central Google Scholar
• Raman, M., Havens, C.G., Walter, J.C. & Harper, J.W. A genome-wide screen identifies p97 as an essential regulator of DNA damage–dependent CDT1 destruction. Mol. Cell 44, 72–84 (2011).
  CAS PubMed PubMed Central Google Scholar
• DeLaBarre, B., Christianson, J.C., Kopito, R.R. & Brunger, A.T. Central pore residues mediate the p97/VCP activity required for ERAD. Mol. Cell 22, 451–462 (2006).
  CAS PubMed Google Scholar
• Husnjak, K. & Dikic, I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu. Rev. Biochem. 81, 291–322 (2012).
  CAS PubMed Google Scholar
• Richly, H. et al. A series of ubiquitin binding factors connects CDC48/p97 to substrate multiubiquitylation and proteasomal targeting. Cell 120, 73–84 (2005).Refs. 61, 62 and 64 defined the role of a class of UBA- and UBL-containing proteins in targeting retrotranslocated products to the proteasome for degradation.
  CAS PubMed Google Scholar
• Verma, R., Oania, R., Graumann, J. & Deshaies, R.J. Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system. Cell 118, 99–110 (2004).
  CAS PubMed Google Scholar
• Kim, I., Mi, K. & Rao, H. Multiple interactions of rad23 suggest a mechanism for ubiquitylated substrate delivery important in proteolysis. Mol. Biol. Cell 15, 3357–3365 (2004).
  CAS PubMed PubMed Central Google Scholar
• Kim, I. et al. The Png1-Rad23 complex regulates glycoprotein turnover. J. Cell Biol. 172, 211–219 (2006).
  CAS PubMed PubMed Central Google Scholar
• Lim, P.J. et al. Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD. J. Cell Biol. 187, 201–217 (2009).
  CAS PubMed PubMed Central Google Scholar
• Hiyama, H. et al. Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome. J. Biol. Chem. 274, 28019–28025 (1999).
  CAS PubMed Google Scholar
• Okuda-Shimizu, Y. & Hendershot, L.M. Characterization of an ERAD pathway for nonglycosylated BiP substrates, which require Herp. Mol. Cell 28, 544–554 (2007).
  CAS PubMed PubMed Central Google Scholar
• Schulze, A. et al. The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway. J. Mol. Biol. 354, 1021–1027 (2005).
  CAS PubMed Google Scholar
• Jo, Y., Sguigna, P.V. & DeBose-Boyd, R.A. Membrane-associated ubiquitin ligase complex containing gp78 mediates sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J. Biol. Chem. 286, 15022–15031 (2011).
  CAS PubMed PubMed Central Google Scholar
• Wang, Q. et al. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble States for proteasome degradation. Mol. Cell 42, 758–770 (2011).This paper demonstrated the involvement of a multifunctional cytosolic chaperone in maintaining the solubility of retrotranslocated polypeptides, which promotes their turnover in mammalian cells.
  CAS PubMed PubMed Central Google Scholar
• Horn, S.C. et al. Usa1 functions as a scaffold of the HRD-ubiquitin ligase. Mol. Cell 36, 782–793 (2009).
  CAS PubMed Google Scholar
• Huang, C.H., Chu, Y.R., Ye, Y. & Chen, X. Role of HERP and a HERP-related protein in HRD1-dependent protein degradation at the endoplasmic reticulum. J. Biol. Chem. 289, 4444–4454 (2014).
  CAS PubMed Google Scholar
• Xu, Y., Liu, Y., Lee, J.G. & Ye, Y. A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation. J. Biol. Chem. 288, 18068–18076 (2013).
  CAS PubMed PubMed Central Google Scholar
• Xu, Y., Cai, M., Yang, Y., Huang, L. & Ye, Y. SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation. Cell Rep. 2, 1633–1644 (2012).
  CAS PubMed PubMed Central Google Scholar
• Vembar, S.S. & Brodsky, J.L. One step at a time: endoplasmic reticulum–associated degradation. Nat. Rev. Mol. Cell Biol. 9, 944–957 (2008).
  CAS PubMed PubMed Central Google Scholar
• Shamu, C.E., Story, C.M., Rapoport, T.A. & Ploegh, H.L. The pathway of US11-dependent degradation of MHC class I heavy chains involves a ubiquitin-conjugated intermediate. J. Cell Biol. 147, 45–58 (1999).
  CAS PubMed PubMed Central Google Scholar
• Burr, M.L. et al. MHC class I molecules are preferentially ubiquitinated on endoplasmic reticulum luminal residues during HRD1 ubiquitin E3 ligase-mediated dislocation. Proc. Natl. Acad. Sci. USA 110, 14290–14295 (2013).
  CAS PubMed PubMed Central Google Scholar
• Fleig, L. et al. Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins. Mol. Cell 47, 558–569 (2012).
  CAS PubMed Google Scholar
• Feige, M.J. & Hendershot, L.M. Quality control of integral membrane proteins by assembly-dependent membrane integration. Mol. Cell 51, 297–309 (2013).
  CAS PubMed PubMed Central Google Scholar
• Bordallo, J., Plemper, R.K., Finger, A. & Wolf, D.H. Der3p/Hrd1p is required for endoplasmic reticulum–associated degradation of misfolded lumenal and integral membrane proteins. Mol. Biol. Cell 9, 209–222 (1998).
  CAS PubMed PubMed Central Google Scholar
• Sato, B.K., Schulz, D., Do, P.H. & Hampton, R.Y. Misfolded membrane proteins are specifically recognized by the transmembrane domain of the Hrd1p ubiquitin ligase. Mol. Cell 34, 212–222 (2009).
  CAS PubMed PubMed Central Google Scholar
• Carvalho, P., Stanley, A.M. & Rapoport, T.A. Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p. Cell 143, 579–591 (2010).Refs. 82 and 106 used an elegant in vivo cross-linking approach to characterize the interactions between a retrotranslocation substrate and the Hrd1p ubiquitin-ligase complex. The evidence suggests that Hrd1p and Der1p play essential parts in substrate recognition and/or retrotranslocation.
  CAS PubMed PubMed Central Google Scholar
• Klemm, E.J., Spooner, E. & Ploegh, H.L. Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control. J. Biol. Chem. 286, 37602–37614 (2011).
  CAS PubMed PubMed Central Google Scholar
• Jo, Y., Hartman, I.Z. & DeBose-Boyd, R.A. Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated endoplasmic reticulum membranes. Mol. Biol. Cell 24, 169–183 (2013).
  CAS PubMed PubMed Central Google Scholar
• Olzmann, J.A., Richter, C.M. & Kopito, R.R. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc. Natl. Acad. Sci. USA 110, 1345–1350 (2013).
  CAS PubMed PubMed Central Google Scholar
• Ploegh, H.L. A lipid-based model for the creation of an escape hatch from the endoplasmic reticulum. Nature 448, 435–438 (2007).
  CAS PubMed Google Scholar
• Olzmann, J.A. & Kopito, R.R. Lipid droplet formation is dispensable for endoplasmic reticulum–associated degradation. J. Biol. Chem. 286, 27872–27874 (2011).
  CAS PubMed PubMed Central Google Scholar
• Duttler, S., Pechmann, S. & Frydman, J. Principles of cotranslational ubiquitination and quality control at the ribosome. Mol. Cell 50, 379–393 (2013).
  CAS PubMed Google Scholar
• Sliter, D.A., Aguiar, M., Gygi, S.P. & Wojcikiewicz, R.J. Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation. J. Biol. Chem. 286, 1074–1082 (2011).
  CAS PubMed Google Scholar
• Li, W., Tu, D., Brunger, A.T. & Ye, Y. A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate. Nature 446, 333–337 (2007).
  CAS PubMed Google Scholar
• Xu, P. et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137, 133–145 (2009).
  CAS PubMed PubMed Central Google Scholar
• Hampton, R.Y. & Sommer, T. Finding the will and the way of ERAD substrate retrotranslocation. Curr. Opin. Cell Biol. 24, 460–466 (2012).
  CAS PubMed Google Scholar
• Wiertz, E.J. et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384, 432–438 (1996).
  CAS PubMed Google Scholar
• Scott, D.C. & Schekman, R. Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins. J. Cell Biol. 181, 1095–1105 (2008).
  CAS PubMed PubMed Central Google Scholar
• Pilon, M., Schekman, R. & Romisch, K. Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation. EMBO J. 16, 4540–4548 (1997).
  CAS PubMed PubMed Central Google Scholar
• Zhou, M. & Schekman, R. The engagement of Sec61p in the ER dislocation process. Mol. Cell 4, 925–934 (1999).
  CAS PubMed Google Scholar
• Van den Berg, B. et al. X-ray structure of a protein-conducting channel. Nature 427, 36–44 (2004).
  CAS PubMed Google Scholar
• Greenblatt, E.J., Olzmann, J.A. & Kopito, R.R. Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum. Nat. Struct. Mol. Biol. 18, 1147–1152 (2011).
  CAS PubMed PubMed Central Google Scholar
• Huang, C.H., Hsiao, H.T., Chu, Y.R., Ye, Y. & Chen, X. Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum. J. Biol. Chem. 288, 25330–25339 (2013).
  CAS PubMed PubMed Central Google Scholar
• Wahlman, J. et al. Real-time fluorescence detection of ERAD substrate retrotranslocation in a mammalian in vitro system. Cell 129, 943–955 (2007).
  CAS PubMed PubMed Central Google Scholar
• Knop, M., Finger, A., Braun, T., Hellmuth, K. & Wolf, D.H. Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. EMBO J. 15, 753–763 (1996).Refs. 101, 102 and 105 reported a family of conserved multispanning membrane proteins essential for retrotranslocation of a subset of ERAD substrates.
  CAS PubMed PubMed Central Google Scholar
• Ye, Y., Shibata, Y., Yun, C., Ron, D. & Rapoport, T.A. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429, 841–847 (2004).
  CAS PubMed Google Scholar
• Kothe, M. et al. Role of p97 AAA-ATPase in the retrotranslocation of the cholera toxin A1 chain, a non-ubiquitinated substrate. J. Biol. Chem. 280, 28127–28132 (2005).
  CAS PubMed Google Scholar
• Gauss, R., Sommer, T. & Jarosch, E. The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment. EMBO J. 25, 1827–1835 (2006).
  CAS PubMed PubMed Central Google Scholar
• Lilley, B.N. & Ploegh, H.L. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429, 834–840 (2004).
  CAS PubMed Google Scholar
• Mehnert, M., Sommer, T. & Jarosch, E. Der1 promotes movement of misfolded proteins through the endoplasmic reticulum membrane. Nat. Cell Biol. 16, 77–86 (2014).
  CAS PubMed Google Scholar
• Gardner, R.G. et al. Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p. J. Cell Biol. 151, 69–82 (2000).
  CAS PubMed PubMed Central Google Scholar
• Foresti, O., Ruggiano, A., Hannibal-Bach, H.K., Ejsing, C.S. & Carvalho, P. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. Elife 2, e00953 (2013).
  PubMed PubMed Central Google Scholar
• Rubenstein, E.M., Kreft, S.G., Greenblatt, W., Swanson, R. & Hochstrasser, M. Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase. J. Cell Biol. 197, 761–773 (2012).
  CAS PubMed PubMed Central Google Scholar
• Xu, S., Peng, G., Wang, Y., Fang, S. & Karbowski, M. The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover. Mol. Biol. Cell 22, 291–300 (2011).
  CAS PubMed PubMed Central Google Scholar
• Bolte, K. et al. Making new out of old: recycling and modification of an ancient protein translocation system during eukaryotic evolution. Mechanistic comparison and phylogenetic analysis of ERAD, SELMA and the peroxisomal importomer. Bioessays 33, 368–376 (2011).
  CAS PubMed Google Scholar
• Barthelme, D. & Sauer, R.T. Identification of the Cdc48•20S proteasome as an ancient AAA+ proteolytic machine. Science 337, 843–846 (2012).
  CAS PubMed PubMed Central Google Scholar
• Isakov, E. & Stanhill, A. Stalled proteasomes are directly relieved by P97 recruitment. J. Biol. Chem. 286, 30274–30283 (2011).
  CAS PubMed PubMed Central Google Scholar
• Verma, R. et al. Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell 11, 3425–3439 (2000).
  CAS PubMed PubMed Central Google Scholar
• Lee, J.G. & Ye, Y. Bag6/Bat3/Scythe: a novel chaperone activity with diverse regulatory functions in protein biogenesis and degradation. Bioessays 35, 377–385 (2013).
  CAS PubMed Google Scholar
• Minami, R. et al. BAG-6 is essential for selective elimination of defective proteasomal substrates. J. Cell Biol. 190, 637–650 (2010).
  CAS PubMed PubMed Central Google Scholar
• Ahner, A., Nakatsukasa, K., Zhang, H., Frizzell, R.A. & Brodsky, J.L. Small heat-shock proteins select deltaF508-CFTR for endoplasmic reticulum-associated degradation. Mol. Biol. Cell 18, 806–814 (2007).
  CAS PubMed PubMed Central Google Scholar
• Grotzke, J.E., Lu, Q. & Cresswell, P. Deglycosylation-dependent fluorescent proteins provide unique tools for the study of ER-associated degradation. Proc. Natl. Acad. Sci. USA 110, 3393–3398 (2013).
  CAS PubMed PubMed Central Google Scholar
• Wang, X., Yu, Y.Y., Myers, N. & Hansen, T.H. Decoupling the role of ubiquitination for the dislocation versus degradation of major histocompatibility complex (MHC) class I proteins during endoplasmic reticulum-associated degradation (ERAD). J. Biol. Chem. 288, 23295–23306 (2013).
  CAS PubMed PubMed Central Google Scholar
• Zhong, Y. & Fang, S. Live cell imaging of protein dislocation from the endoplasmic reticulum. J. Biol. Chem. 287, 28057–28066 (2012).
  CAS PubMed PubMed Central Google Scholar
• Metzger, M.B. et al. A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms. Mol. Cell 50, 516–527 (2013).
  CAS PubMed PubMed Central Google Scholar
• Kostova, Z., Mariano, J., Scholz, S., Koenig, C. & Weissman, A.M.A. Ubc7p-binding domain in Cue1p activates ER-associated protein degradation. J. Cell Sci. 122, 1374–1381 (2009).
  CAS PubMed PubMed Central Google Scholar
• Das, R. et al. Allosteric activation of E2-RING finger–mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Mol. Cell 34, 674–685 (2009).
  CAS PubMed PubMed Central Google Scholar
• Li, W. et al. Mechanistic insights into active site–associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2. Proc. Natl. Acad. Sci. USA 106, 3722–3727 (2009).
  CAS PubMed PubMed Central Google Scholar
• Bagola, K. et al. Ubiquitin binding by a CUE domain regulates ubiquitin chain formation by ERAD E3 ligases. Mol. Cell 50, 528–539 (2013).
  CAS PubMed Google Scholar
• Liu, S. et al. Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains. Structure 20, 2138–2150 (2012).
  CAS PubMed PubMed Central Google Scholar
• Chen, B. et al. The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site. Proc. Natl. Acad. Sci. USA 103, 341–346 (2006).
  CAS PubMed PubMed Central Google Scholar
• Koegl, M. et al. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96, 635–644 (1999).
  CAS PubMed Google Scholar
• Hatakeyama, S., Yada, M., Matsumoto, M., Ishida, N. & Nakayama, K.I. U box proteins as a new family of ubiquitin-protein ligases. J. Biol. Chem. 276, 33111–33120 (2001).
  CAS PubMed Google Scholar
• Nakatsukasa, K., Huyer, G., Michaelis, S. & Brodsky, J.L. Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell 132, 101–112 (2008).
  CAS PubMed PubMed Central Google Scholar
• Meacham, G.C., Patterson, C., Zhang, W., Younger, J.M. & Cyr, D.M. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3, 100–105 (2001).
  CAS PubMed Google Scholar