The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation (original) (raw)
Wilkinson, K. D. The discovery of ubiquitin-dependent proteolysis. Proc. Natl Acad. Sci. USA102, 15280–15282 (2005). CASPubMedPubMed Central Google Scholar
Shabek, N., Iwai, K. & Ciechanover, A. Ubiquitin is degraded by the ubiquitin system as a monomer and as part of its conjugated target. Biochem. Biophys. Res. Commun.363, 425–431 (2007). CASPubMed Google Scholar
Hershko, A., Eytan, E., Ciechanover, A. & Haas, A. L. Immunochemical analysis of the turnover of ubiquitin-protein conjugates in intact cells. Relationship to the breakdown of abnormal proteins. J. Biol. Chem.257, 13964–13970 (1982). The first description of the role of the ubiquitin proteolytic system in the degradation of proteins in intact nucleated cells. All prior studies describing the roles of the system were carried out using reticulocytes and mostly cell-free extracts from these cells, which are terminally differentiating red blood cells. CASPubMed Google Scholar
Haas, A. L. & Bright, P. M. The dynamics of ubiquitin pools within cultured human lung fibroblasts. J. Biol. Chem.262, 345–351 (1987). CASPubMed Google Scholar
Patel, M. B. & Majetschak, M. Distribution and interrelationship of ubiquitin proteasome pathway component activities and ubiquitin pools in various porcine tissues. Physiol. Res.56, 341–350 (2007). CASPubMed Google Scholar
Ciechanover, A., Elias, S., Heller, H., Ferber, S. & Hershko, A. Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. J. Biol. Chem.255, 7525–7528 (1980). The first detailed characterization of ubiquitin. CASPubMed Google Scholar
Vijay-Kumar, S., Bugg, C. E. & Cook, W. J. Structure of ubiquitin refined at 1.8 Å resolution. J. Mol. Biol.194, 531–544 (1987). Detailed three-dimensional structure of ubiquitin. CASPubMed Google Scholar
Carlson, N. & Rechsteiner, M. Microinjection of ubiquitin: intracellular distribution and metabolism in HeLa cells maintained under normal physiological conditions. J. Cell Biol.104, 537–546 (1987). CASPubMed Google Scholar
Hiroi, Y. & Rechsteiner, M. Ubiquitin metabolism in HeLa cells starved of amino acids. FEBS Lett.307, 156–161 (1992). CASPubMed Google Scholar
Leggett, D. S. et al. Multiple associated proteins regulate proteasome structure and function. Mol. Cell10, 495–507 (2002). Describes Ubp6 as a proteasome-associated DUB and details its role in controlling cellular ubiquitin levels and proteasomal degradation by balancing the deubiquitylating and proteolytic activities of the protease. CASPubMed Google Scholar
Shabek, N., Herman-Bachinsky, Y. & Ciechanover, A. Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation. Proc. Natl Acad. Sci. USA106, 11907–11912 (2009). Description of degradation of ubiquitin as a monomer, as a C-terminally extended molecule and as part of the substrate-anchored polyubiquitin chain. CASPubMedPubMed Central Google Scholar
Verhoef, L. G. et al. Minimal length requirement for proteasomal degradation of ubiquitin-dependent substrates. FASEB J.23, 123–133 (2009). Describes the C-terminal extension tail as a ubiquitin-destabilizing element. CASPubMed Google Scholar
Piotrowski, J. et al. Inhibition of the 26S proteasome by polyubiquitin chains synthesized to have defined lengths. J. Biol. Chem.272, 23712–23721 (1997). CASPubMed Google Scholar
Park, Y., Yoon, S. K. & Yoon, J. B. The HECT domain of TRIP12 ubiquitinates substrates of the ubiquitin fusion degradation pathway. J. Biol. Chem.284, 1540–1549 (2009). CASPubMed Google Scholar
Xia, Z. P. et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature461, 114–119 (2009). CASPubMedPubMed Central Google Scholar
Kimura, Y. et al. An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis. Cell137, 549–559 (2009). CASPubMed Google Scholar
Anderson, C. et al. Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice. J. Neurochem.95, 724–731 (2005). CASPubMed Google Scholar
Hanna, J., Leggett, D. S. & Finley, D. Ubiquitin depletion as a key mediator of toxicity by translational inhibitors. Mol. Cell. Biol.23, 9251–9261 (2003). CASPubMedPubMed Central Google Scholar
Verma, R. et al. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science298, 611–615 (2002). CASPubMed Google Scholar
Lee, M. J., Lee, B. H., Hanna, J., King, R. W. & Finley, D. Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol. Cell Proteomics10, R110.003871 (2011). PubMed Google Scholar
Hanna, J., Meides, A., Zhang, D. P. & Finley, D. A ubiquitin stress response induces altered proteasome composition. Cell129, 747–759 (2007). Demonstrates that ubiquitin stress induces Ubp6, which rescues ubiquitin from target substrates, thus helping to restore ubiquitin homeostasis. CASPubMed Google Scholar
Hanna, J. et al. Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell127, 99–111 (2006). CASPubMed Google Scholar
Peth, A., Uchiki, T. & Goldberg, A. L. ATP-dependent steps in the binding of ubiquitin conjugates to the 26S proteasome that commit to degradation. Mol. Cell40, 671–681 (2010). CASPubMedPubMed Central Google Scholar
Kumar, K. S., Spasser, L., Ohayon, S., Erlich, L. A. & Brik, A. Expeditious chemical synthesis of ubiquitinated peptides employing orthogonal protection and native chemical ligation. Bioconjug. Chem.22, 137–143 (2011). Describes a novel synthetic method to generate peptides and proteins to which ubiquitin is attached by an isopeptide bond to a Lys residue that can be inserted at any point of choice along the chain. CASPubMed Google Scholar
Ciechanover, A. & Ben-Saadon, R. N-terminal ubiquitination: more protein substrates join in. Trends Cell Biol.14, 103–106 (2004). CASPubMed Google Scholar
Papa, F. R. & Hochstrasser, M. The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Nature366, 313–319 (1993). CASPubMed Google Scholar
Dupre, S. & Haguenauer-Tsapis, R. Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins: crucial role of Doa4p ubiquitin isopeptidase. Mol. Cell. Biol.21, 4482–4494 (2001). CASPubMedPubMed Central Google Scholar
Prakash, S., Inobe, T., Hatch, A. J. & Matouschek, A. Substrate selection by the proteasome during degradation of protein complexes. Nature Chem. Biol.5, 29–36 (2009). Establishes that two elements are critical for the proteasome to recognize and degrade a target substrate — conjugated ubiquitin and an unstructured tail in the substrate that will allow its entry into the 20S CP. CAS Google Scholar
van Leeuwen, F. W., Hol, E. M. & Fischer, D. F. Frameshift proteins in Alzheimer's disease and in other conformational disorders: time for the ubiquitin-proteasome system. J. Alzheimers Dis.9, 319–325 (2006). Describes the naturally occurring C-terminally extended ubiquitin UBB+1, which inhibits the proteasome as it binds to it but, owing to its tail, which is too short (19 residues), cannot be degraded. CASPubMed Google Scholar
Lam, Y. A. et al. Inhibition of the ubiquitin-proteasome system in Alzheimer's disease. Proc. Natl Acad. Sci. USA97, 9902–9906 (2000). CASPubMedPubMed Central Google Scholar
Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl Acad. Sci. USA96, 11364–11369 (1999). Establishes that RING finger proteins are generally E3s and that they can mediate self-ubiquitylationin vitro. CASPubMedPubMed Central Google Scholar
Ravid, T. & Hochstrasser, M. Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue. Nature Cell Biol.9, 422–427 (2007). CASPubMed Google Scholar
Dikic, I., Wakatsuki, S. & Walters, K. J. Ubiquitin-binding domains — from structures to functions. Nature Rev. Mol. Cell Biol.10, 659–671 (2009). CAS Google Scholar
Wade, M., Wang, Y. V. & Wahl, G. M. The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol.20, 299–309 (2010). CASPubMedPubMed Central Google Scholar
Lee, J. T. & Gu, W. The multiple levels of regulation by p53 ubiquitination. Cell Death Differ.17, 86–92 (2010). CASPubMed Google Scholar
Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H. & Weissman, A. M. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem.275, 8945–8951 (2000). CASPubMed Google Scholar
Honda, R. & Yasuda, H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene19, 1473–1476 (2000). References36and37establish that MDM2 can target itself for ubiquitylation through its RING finger. CASPubMed Google Scholar
Linke, K. et al. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ.15, 841–848 (2008). CASPubMed Google Scholar
Tanimura, S. et al. MDM2 interacts with MDMX through their RING finger domains. FEBS Lett.447, 5–9 (1999). CASPubMed Google Scholar
Linares, L. K., Hengstermann, A., Ciechanover, A., Muller, S. & Scheffner, M. HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc. Natl Acad. Sci. USA100, 12009–12014 (2003). CASPubMedPubMed Central Google Scholar
Okamoto, K., Taya, Y. & Nakagama, H. Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase. FEBS Lett.583, 2710–2714 (2009). CASPubMed Google Scholar
Cummins, J. M. & Vogelstein, B. HAUSP is required for p53 destabilization. Cell Cycle3, 689–692 (2004). CASPubMed Google Scholar
Li, M., Brooks, C. L., Kon, N. & Gu, W. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol. Cell13, 879–886 (2004). CASPubMed Google Scholar
Meulmeester, E., Pereg, Y., Shiloh, Y. & Jochemsen, A. G. ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle4, 1166–1170 (2005). CASPubMed Google Scholar
Meulmeester, E. et al. Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Mol. Cell18, 565–576 (2005). References43, 44, 45, 46establish the deubiquitylation of MDM2 and MDMX by the DUB USP7 and the significance of regulation of this association in response to genotoxic stress. CASPubMed Google Scholar
Acconcia, F., Sigismund, S. & Polo, S. Ubiquitin in trafficking: the network at work. Exp. Cell Res.315, 1610–1618 (2009). CASPubMed Google Scholar
Rotin, D. & Kumar, S. Physiological functions of the HECT family of ubiquitin ligases. Nature Rev. Mol. Cell Biol.10, 398–409 (2009). CAS Google Scholar
Macias, M. J., Wiesner, S. & Sudol, M. WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett.513, 30–37 (2002). CASPubMed Google Scholar
Ryan, P. E., Davies, G. C., Nau, M. M. & Lipkowitz, S. Regulating the regulator: negative regulation of Cbl ubiquitin ligases. Trends Biochem. Sci.31, 79–88 (2006). CASPubMed Google Scholar
Kales, S. C., Ryan, P. E., Nau, M. M. & Lipkowitz, S. Cbl and human myeloid neoplasms: the Cbl oncogene comes of age. Cancer Res.70, 4789–4794 (2010). CASPubMedPubMed Central Google Scholar
Davies, G. C. et al. Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. Oncogene23, 7104–7115 (2004). CASPubMed Google Scholar
Ettenberg, S. A. et al. Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. J. Biol. Chem.276, 27677–27684 (2001). CASPubMed Google Scholar
Magnifico, A. et al. WW domain HECT E3s target Cbl RING finger E3s for proteasomal degradation. J. Biol. Chem.278, 43169–43177 (2003). References53and54, respectively, establish the RTK-mediated down regulation of CBL proteins by self-ubiquitylation and their ubiquitylation by NEDD4 family members. Reference54is the first clear example of the targeting of one E3 family by another. CASPubMed Google Scholar
Yang, B. et al. Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells. Nature Immunol.9, 1356–1363 (2008). CAS Google Scholar
Gay, D. L., Ramon, H. & Oliver, P. M. Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity. Immunol. Res.42, 51–64 (2008). CASPubMedPubMed Central Google Scholar
Gallagher, E., Gao, M., Liu, Y. C. & Karin, M. Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change. Proc. Natl Acad. Sci. USA103, 1717–1722 (2006). CASPubMedPubMed Central Google Scholar
Azakir, B. A. & Angers, A. Reciprocal regulation of the ubiquitin ligase Itch and the epidermal growth factor receptor signaling. Cell. Signal.21, 1326–1336 (2009). CASPubMed Google Scholar
Mouchantaf, R. et al. The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. J. Biol. Chem.281, 38738–38747 (2006). CASPubMed Google Scholar
Tsai, Y. C. & Weissman, A. M. The unfolded protein response, degradation from endoplasmic reticulum and cancer. Genes Cancer1, 764–778 (2010). CASPubMedPubMed Central Google Scholar
Fang, S. et al. The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proc. Natl Acad. Sci. USA98, 14422–14427 (2001). CASPubMedPubMed Central Google Scholar
Tsai, Y. C. et al. The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nature Med.13, 1504–1509 (2007). CASPubMed Google Scholar
Morito, D. et al. Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRδF508. Mol. Biol. Cell19, 1328–1336 (2008). CASPubMedPubMed Central Google Scholar
Ye, Y. et al. Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane. Proc. Natl Acad. Sci. USA102, 14132–14138 (2005). CASPubMedPubMed Central Google Scholar
Lee, J. N., Song, B., DeBose-Boyd, R. A. & Ye, J. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J. Biol. Chem.281, 39308–39315 (2006). CASPubMed 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. USA103, 341–346 (2006). CASPubMedPubMed 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. Cell34, 674–685 (2009). CASPubMedPubMed Central Google Scholar
Shmueli, A., Tsai, Y. C., Yang, M., Braun, M. A. & Weissman, A. M. Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum. Biochem. Biophys. Res. Commun.390, 758–762 (2009). CASPubMedPubMed Central Google Scholar
Ballar, P., Ors, A. U., Yang, H. & Fang, S. Differential regulation of CFTRΔF508 degradation by ubiquitin ligases gp78 and Hrd1. Int. J. Biochem. Cell Biol.42, 167–173 (2010). Reference68and69describe the regulation of the pro-metastatic ERAD E3 gp78 by HRD1. CASPubMed 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). CASPubMedPubMed Central Google Scholar
Iida, Y. et al. SEL1L protein critically determines the stability of the HRD1-SEL1L endoplasmic reticulum-associated degradation (ERAD) complex to optimize the degradation kinetics of ERAD substrates. J. Biol. Chem.286, 16929–16939 (2011). CASPubMedPubMed Central Google Scholar
Carroll, S. M. & Hampton, R. Y. Usa1p is required for optimal function and regulation of the Hrd1p endoplasmic reticulum-associated degradation ubiquitin ligase. J. Biol. Chem.285, 5146–5156 (2010). Shows that the critical yeast ERAD E3 Hrd1 undergoes self-ubiquitylation intransin a manner that is regulated by a relative lack of Hrd3 and the presence of Usa1, both of which are components of the Hrd1 ubiquitin ligase complex. CASPubMed Google Scholar
Horn, S. C. et al. Usa1 functions as a scaffold of the HRD-ubiquitin ligase. Mol. Cell36, 782–793 (2009). CASPubMed Google Scholar
Cao, R. et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science298, 1039–1043 (2002). CASPubMed Google Scholar
Ben-Saadon, R., Zaaroor, D., Ziv, T. & Ciechanover, A. The polycomb protein RING1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. Mol. Cell24, 701–711 (2006). Establishes that RING1B undergoes self-ubiquitylation with the formation of multiply branched chains that do not target it for degradation but rather activate the ligase. CASPubMed Google Scholar
Kim, H. T., Kim, K. P., Uchiki, T., Gygi, S. P. & Goldberg, A. L. S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains. EMBO J.28, 1867–1877 (2009). CASPubMedPubMed Central Google Scholar
Zaaroor-Regev, D. et al. Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. Proc. Natl Acad. Sci. USA107, 6788–6793 (2010). Demonstrates that the stability of RING1B is regulated by heterologous ligases, including the HECT domain E3 E6AP. CASPubMedPubMed Central Google Scholar
Bernassola, F., Ciechanover, A. & Melino, G. The ubiquitin proteasome system and its involvement in cell death pathways. Cell Death Differ.17, 1–3 (2010). CASPubMed Google Scholar
Vucic, D., Dixit, V. M. & Wertz, I. E. Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nature Rev. Mol. Cell Biol.12, 439–452 (2011). CAS Google Scholar
Yang, Y., Fang, S., Jensen, J. P., Weissman, A. M. & Ashwell, J. D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science288, 874–877 (2000). Demonstrates that the activation of IAPs by steroids leads to auto-ubiquitylation and the induction of apoptosis. Provides a mechanistic description of the deleterious effect of steroids on lymphocytes. CASPubMed Google Scholar
Ditzel, M. et al. Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis. Nature Cell Biol.5, 467–473 (2003). CASPubMed Google Scholar
Ryoo, H. D., Bergmann, A., Gonen, H., Ciechanover, A. & Steller, H. Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. Nature Cell Biol.4, 432–438 (2002). Establishes that one mechanism of induction of apoptosis by the small protein Reaper is via its ability to bind and induce self-ubiquitylation and subsequent degradation ofD. melanogasterIAP1. CASPubMed Google Scholar
Herman-Bachinsky, Y., Ryoo, H. D., Ciechanover, A. & Gonen, H. Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several distinct ubiquitin system pathways. Cell Death Differ.14, 861–871 (2007). CASPubMed Google Scholar
Steller, H. Regulation of apoptosis in Drosophila. Cell Death Differ.15, 1132–1138 (2008). CASPubMed Google Scholar
Wing, J. P. et al. Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis. Nature Cell Biol.4, 451–456 (2002). CASPubMed Google Scholar
Fu, J., Jin, Y. & Arend, L. J. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J. Biol. Chem.278, 52660–52672 (2003). CASPubMed Google Scholar
Silke, J., Kratina, T., Ekert, P. G., Pakusch, M. & Vaux, D. L. Unlike Diablo/Smac, Grim promotes global ubiquitination and specific degradation of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis. J. Biol. Chem.279, 4313–4321 (2004). CASPubMed Google Scholar
Garrison, J. B. et al. ARTS and Siah collaborate in a pathway for XIAP degradation. Mol. Cell41, 107–116 (2011). CASPubMed Google Scholar
Finley, D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem.78, 477–513 (2009). CASPubMedPubMed Central Google Scholar
Cuervo, A. M., Palmer, A., Rivett, A. J. & Knecht, E. Degradation of proteasomes by lysosomes in rat liver. Eur. J. Biochem.227, 792–800 (1995). CASPubMed Google Scholar
Isasa, M. et al. Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome. Mol. Cell38, 733–745 (2010). CASPubMedPubMed Central Google Scholar
Panasenko, O. O. & Collart, M. A. Not4 E3 ligase contributes to proteasome assembly and functional integrity in part through Ecm29. Mol. Cell. Biol.31, 1610–1623 (2011). CASPubMedPubMed Central Google Scholar
Holic, R. et al. Cks1 activates transcription by binding to the ubiquitylated proteasome. Mol. Cell. Biol.30, 3894–3901 (2010). CASPubMedPubMed Central Google Scholar
Tai, H. C., Besche, H., Goldberg, A. L. & Schuman, E. M. Characterization of the brain 26S proteasome and its interacting proteins. Front. Mol. Neurosci.3, 12 (2010). A detailed analysis of the brain proteasome and its regulation by different stimuli, such as oxidative stress and NMDA receptor activity. PubMedPubMed Central Google Scholar
Peth, A., Besche, H. C. & Goldberg, A. L. Ubiquitinated proteins activate the proteasome by binding to Usp14/Ubp6, which causes 20S gate opening. Mol. Cell36, 794–804 (2009). CASPubMedPubMed Central Google Scholar
Bech-Otschir, D. et al. Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome. Nature Struct. Mol. Biol.16, 219–225 (2009). CAS Google Scholar
Sun, X. M. et al. Caspase activation inhibits proteasome function during apoptosis. Mol. Cell14, 81–93 (2004). Describes the regulation of the proteasome during apoptosis. CASPubMed Google Scholar
Wang, X. H. et al. Caspase-3 cleaves specific 19S proteasome subunits in skeletal muscle stimulating proteasome activity. J. Biol. Chem.285, 21249–21257 (2010). CASPubMedPubMed Central Google Scholar
Wang, X., Yen, J., Kaiser, P. & Huang, L. Regulation of the 26S proteasome complex during oxidative stress. Sci. Signal.3, ra88 (2010). CASPubMedPubMed Central Google Scholar
Medicherla, B. & Goldberg, A. L. Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins. J. Cell Biol.182, 663–673 (2008). CASPubMedPubMed Central Google Scholar
Bajorek, M., Finley, D. & Glickman, M. H. Proteasome disassembly and downregulation is correlated with viability during stationary phase. Curr. Biol.13, 1140–1144 (2003). Describes the regulation of the proteasome by starvation. CASPubMed Google Scholar
Peters, J. M. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nature Rev. Mol. Cell Biol.7, 644–656 (2006). CAS Google Scholar
Manchado, E., Eguren, M. & Malumbres, M. The anaphase-promoting complex/cyclosome (APC/C): cell-cycle-dependent and -independent functions. Biochem. Soc. Trans.38, 65–71 (2010). CASPubMed Google Scholar
Carrano, A. C., Eytan, E., Hershko, A. & Pagano, M. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nature Cell Biol.1, 193–199 (1999). CASPubMed Google Scholar
Sutterluty, H. et al. p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nature Cell Biol.1, 207–214 (1999). CASPubMed Google Scholar
Tsvetkov, L. M., Yeh, K. H., Lee, S. J., Sun, H. & Zhang, H. p27Kip1 ubiquitination and degradation is regulated by the SCFSkp2 complex through phosphorylated Thr187 in p27. Curr. Biol.9, 661–664 (1999). CASPubMed Google Scholar
Bashir, T., Dorrello, N. V., Amador, V., Guardavaccaro, D. & Pagano, M. Control of the SCFSkp2–Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase. Nature428, 190–193 (2004). References106and107establish that S phase kinase-associated protein 2 (SKP2) is targeted for degradation by the APC/C. CASPubMed Google Scholar
Wei, W. et al. Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature428, 194–198 (2004). CASPubMed Google Scholar
Yamanaka, A. et al. Cell cycle-dependent expression of mammalian E2-C regulated by the anaphase-promoting complex/cyclosome. Mol. Biol. Cell11, 2821–2831 (2000). Provides an example of cell cycle-dependent degradation of an E2 as a means to inactive its cognate E3. CASPubMedPubMed Central Google Scholar
Listovsky, T. et al. Mammalian Cdh1/Fzr mediates its own degradation. EMBO J.23, 1619–1626 (2004). Establishes a role for the CDH1 component of the APC/C in its own cell cycle-dependent degradation. CASPubMedPubMed Central Google Scholar
Benmaamar, R. & Pagano, M. Involvement of the SCF complex in the control of Cdh1 degradation in S-phase. Cell Cycle4, 1230–1232 (2005). CASPubMed Google Scholar
Hsu, J. Y., Reimann, J. D., Sorensen, C. S., Lukas, J. & Jackson, P. K. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1. Nature Cell Biol.4, 358–366 (2002). CASPubMed Google Scholar
Reimann, J. D., Gardner, B. E., Margottin-Goguet, F. & Jackson, P. K. Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. Genes Dev.15, 3278–3285 (2001). CASPubMedPubMed Central Google Scholar
Reimann, J. D. et al. Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell105, 645–655 (2001). CASPubMed Google Scholar
Di Fiore, B. & Pines, J. Defining the role of Emi1 in the DNA replication-segregation cycle. Chromosoma117, 333–338 (2008). CASPubMed Google Scholar
Guardavaccaro, D. et al. Control of meiotic and mitotic progression by the F box protein β-Trcp1 in vivo. Dev. Cell4, 799–812 (2003). CASPubMed Google Scholar
Margottin-Goguet, F. et al. Prophase destruction of Emi1 by the SCFβTrCP/Slimb ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev. Cell4, 813–826 (2003). References116and117establish that the APC/C pseudosubstrate and inhibitor EMI1 is targeted for degradation by SCFβ-TrCP. CASPubMed Google Scholar
Moshe, Y., Boulaire, J., Pagano, M. & Hershko, A. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc. Natl Acad. Sci. USA101, 7937–7942 (2004). CASPubMedPubMed Central Google Scholar
Hansen, D. V., Loktev, A. V., Ban, K. H. & Jackson, P. K. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFβTrCP-dependent destruction of the APC inhibitor Emi1. Mol. Biol. Cell15, 5623–5634 (2004). CASPubMedPubMed Central Google Scholar
Xu, P. et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell137, 133–145 (2009). CASPubMedPubMed Central Google Scholar
Matsumoto, M. L. et al. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell39, 477–484 (2010). CASPubMed Google Scholar
Saeki, Y. et al. Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome. EMBO J.28, 359–371 (2009). CASPubMedPubMed Central Google Scholar
Carvalho, A. F. et al. Ubiquitination of mammalian Pex5p, the peroxisomal import receptor. J. Biol. Chem.282, 31267–31272 (2007). CASPubMed Google Scholar
Cadwell, K. & Coscoy, L. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science309, 127–130 (2005). CASPubMed 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). CASPubMedPubMed 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). CASPubMedPubMed Central Google Scholar
Williams, C., van den Berg, M., Sprenger, R. R. & Distel, B. A conserved cysteine is essential for Pex4p-dependent ubiquitination of the peroxisomal import receptor Pex5p. J. Biol. Chem.282, 22534–22543 (2007). CASPubMed Google Scholar
Tait, S. W. et al. Apoptosis induction by Bid requires unconventional ubiquitination and degradation of its N-terminal fragment. J. Cell Biol.179, 1453–1466 (2007). CASPubMedPubMed Central Google Scholar
Shimizu, Y., Okuda-Shimizu, Y. & Hendershot, L. M. Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids. Mol. Cell40, 917–926 (2010). CASPubMedPubMed Central Google Scholar
Scheffner, M., Huibregtse, J. M., Vierstra, R. D. & Howley, P. M. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell75, 495–505 (1993). CASPubMed Google Scholar
Nuber, U., Schwarz, S. E. & Scheffner, M. The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate. Eur. J. Biochem.254, 643–649 (1998). CASPubMed Google Scholar
Hassink, G. et al. TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem. J.388, 647–655 (2005). CASPubMedPubMed Central Google Scholar
Wang, L. et al. Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II. Hepatology48, 1558–1569 (2008). CASPubMed Google Scholar
Zavacki, A. M. et al. The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase. Mol. Cell. Biol.29, 5339–5347 (2009). CASPubMedPubMed Central Google Scholar
Zhou, P. & Howley, P. M. Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol. Cell2, 571–580 (1998). CASPubMed Google Scholar
Li, X., Yang, Y. & Ashwell, J. D. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature416, 345–347 (2002). PubMed Google Scholar
Wu, W. et al. HERC2 is an E3 ligase that targets BRCA1 for degradation. Cancer Res.70, 6384–6392 (2010). CASPubMed Google Scholar
Kee, Y., Kim, J. M. & D'Andrea, A. D. Regulated degradation of FANCM in the Fanconi anemia pathway during mitosis. Genes Dev.23, 555–560 (2009). Establishes that a critical component (FANCM) of the Fanconi anaemia ubiquitin ligase is targeted for degradation by SCFβ-TrCPas a way of inactivating the E3 during mitosis and preventing chromosomal abnormalities. CASPubMedPubMed Central Google Scholar
Lilley, C. E. et al. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. EMBO J.29, 943–955 (2010). Provides an example of how a virally-encoded E3 targets critical RING finger E3s involved in the DNA damage response for degradation. CASPubMedPubMed Central Google Scholar
Nathan, J. A. et al. The ubiquitin E3 ligase MARCH7 is differentially regulated by the deubiquitylating enzymes USP7 and USP9X. Traffic9, 1130–1145 (2008). CASPubMedPubMed Central Google Scholar
Wada, K. & Kamitani, T. Autoantigen Ro52 is an E3 ubiquitin ligase. Biochem. Biophys. Res. Commun.339, 415–421 (2006). CASPubMed Google Scholar
Wada, K., Niida, M., Tanaka, M. & Kamitani, T. Ro52-mediated monoubiquitination of IKKβ down-regulates NF-κB signalling. J. Biochem.146, 821–832 (2009). CASPubMedPubMed Central Google Scholar
Shen, C. et al. Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6. J. Biol. Chem.280, 35967–35973 (2005). CASPubMed Google Scholar
Meray, R. K. & Lansbury, P. T. J. Reversible monoubiquitination regulates the Parkinson disease-associated ubiquitin hydrolase UCH-L1. J. Biol. Chem.282, 10567–10575 (2007). CASPubMed Google Scholar
Todi, S. V. et al. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J.28, 372–382 (2009). CASPubMedPubMed Central Google Scholar
Todi, S. V. et al. Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. J. Biol. Chem.285, 39303–39313 (2010). CASPubMedPubMed Central Google Scholar
Ying, Z. et al. Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Hum. Mol. Genet.18, 4268–4281 (2009). CASPubMed Google Scholar
Wada, K. & Kamitani, T. UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself. Biochem. Biophys. Res. Commun.342, 253–258 (2006). CASPubMed Google Scholar
Boutell, C., Canning, M., Orr, A. & Everett, R. D. Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7. J. Virol.79, 12342–12354 (2005). CASPubMedPubMed Central Google Scholar
Lee, H. J., Kim, M. S., Kim, Y. K., Oh, Y. K. & Baek, K. H. HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized. FEBS Lett.579, 4867–4872 (2005). CASPubMed Google Scholar
Denuc, A., Bosch-Comas, A., Gonzalez-Duarte, R. & Marfany, G. The UBA-UIM domains of the USP25 regulate the enzyme ubiquitination state and modulate substrate recognition. PLoS ONE4, e5571 (2009). PubMedPubMed Central Google Scholar
Bazirgan, O. A. & Hampton, R. Y. Cue1p is an activator of Ubc7p E2 activity in vitro and in vivo. J. Biol. Chem.283, 12797–12810 (2008). CASPubMedPubMed 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). CASPubMedPubMed Central Google Scholar
Kreft, S. G. & Hochstrasser, M. An unusual transmembrane helix in the Doa10 ERAD ubiquitin ligase modulates degradation of its cognate E2. J. Biol. Chem.286, 20163–20174 (2011). CASPubMedPubMed Central Google Scholar
Ho, C. W., Chen, H. T. & Hwang, J. UBC9 autosumoylation negatively regulates sumoylation of septins in Saccharomyces cerevisiae. J. Biol. Chem.286, 21826–21834 (2011). CASPubMedPubMed Central Google Scholar
Pichler, A. et al. SUMO modification of the ubiquitin-conjugating enzyme E2–25K. Nature Struct. Mol. Biol.12, 264–269 (2005). CAS Google Scholar
Duda, D. M. et al. Structural regulation of cullin-RING ubiquitin ligase complexes. Curr. Opin. Struct. Biol.21, 257–264 (2011). CASPubMedPubMed Central Google Scholar