Hicke, L. & Dunn, R. Regulation of membrane protein transport by ubiquitin and ubiquitin–binding proteins. Annu. Rev. Cell Dev. Biol.19, 141–172 (2003). ArticleCASPubMed Google Scholar
Xu, P. et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell137, 133–145 (2009). Google Scholar
Li, W. et al. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS ONE3, e1487 (2008). ArticleCASPubMedPubMed Central Google Scholar
Huibregtse, J. M., Scheffner, M., Beaudenon, S. & Howley, P. M. A family of proteins structurally and functionally related to the E6-AP ubiquitin–protein ligase. Proc. Natl Acad. Sci. USA92, 2563–2567 (1995). The first identification of the HECT family of E3 ligases. ArticleCASPubMedPubMed Central Google Scholar
Kumar, S., Tomooka, Y. & Noda, M. Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem. Biophys. Res. Commun.185, 1155–1161 (1992). ArticleCASPubMed Google Scholar
Plant, P. J. et al. Apical membrane targeting of Nedd4 is mediated by an association of its C2 domain with annexin XIIIb. J. Cell Biol.149, 1473–1484 (2000). ArticleCASPubMedPubMed Central Google Scholar
Dunn, R., Klos, D. A., Adler, A. S. & Hicke, L. The C2 domain of the Rsp5 ubiquitin ligase binds membrane phosphoinositides and directs ubiquitination of endosomal cargo. J. Cell Biol.165, 135–144 (2004). ArticleCASPubMedPubMed Central Google Scholar
Wiesner, S. et al. Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell130, 651–662 (2007). ArticleCASPubMed Google Scholar
Staub, O. et al. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J.15, 2371–2380 (1996). Describes the discovery of the first substrate for a mammalian Nedd4 family member. ArticleCASPubMedPubMed Central Google Scholar
Kanelis, V., Rotin, D. & Forman-Kay, J. D. Solution structure of a Nedd4 WW domain–ENaC peptide complex. Nature Struct. Biol.8, 407–412 (2001). ArticleCASPubMed Google Scholar
Garcia-Gonzalo, F. R. & Rosa, J. L. The HERC proteins: functional and evolutionary insights. Cell. Mol. Life Sci.62, 1826–1838 (2005). ArticleCASPubMed Google Scholar
Renault, L., Kuhlmann, J., Henkel, A. & Wittinghofer, A. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell105, 245–255 (2001). ArticleCASPubMed Google Scholar
Huang, L. et al. Structure of an E6AP–UbcH7 complex: insights into ubiquitination by the E2–E3 enzyme cascade. Science286, 1321–1326 (1999). Deciphers the first structure of a HECT domain. ArticleCASPubMed Google Scholar
Verdecia, M. A. et al. Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. Mol. Cell11, 249–259 (2003). ArticleCASPubMed Google Scholar
Ogunjimi, A. A. et al. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol. Cell19, 297–308 (2005). ArticleCASPubMed Google Scholar
Wang, M. & Pickart, C. M. Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis. EMBO J.24, 4324–4333 (2005). ArticleCASPubMedPubMed Central Google Scholar
Wang, M., Cheng, D., Peng, J. & Pickart, C. M. Molecular determinants of polyubiquitin linkage selection by an HECT ubiquitin ligase. EMBO J.25, 1710–1719 (2006). ArticleCASPubMedPubMed Central Google Scholar
Fisk, H. A. & Yaffe, M. P. A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae. J. Cell Biol.145, 1199–1208 (1999). ArticleCASPubMedPubMed Central Google Scholar
Huibregtse, J. M., Yang, J. C. & Beaudenon, S. L. The large subunit of RNA polymerase II is a substrate of the Rsp5 ubiquitin–protein ligase. Proc. Natl Acad. Sci. USA94, 3656–3661 (1997). ArticleCASPubMedPubMed Central Google Scholar
Somesh, B. P. et al. Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTD. Cell129, 57–68 (2007). ArticleCASPubMed Google Scholar
Dupre, S., Urban-Grimal, D. & Haguenauer-Tsapis, R. Ubiquitin and endocytic internalization in yeast and animal cells. Biochim. Biophys. Acta1695, 89–111 (2004). ArticleCASPubMed Google Scholar
Belgareh-Touze, N. et al. Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking. Biochem. Soc. Trans.36, 791–796 (2008). ArticleCASPubMed Google Scholar
Helliwell, S. B., Losko, S. & Kaiser, C. A. Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease. J. Cell Biol.153, 649–662 (2001). ArticleCASPubMedPubMed Central Google Scholar
Galan, J. M. & Haguenauer-Tsapis, R. Ubiquitin Lys63 is involved in ubiquitination of a yeast plasma membrane protein. EMBO J.16, 5847–5854 (1997). ArticleCASPubMedPubMed Central Google Scholar
Shih, S. C., Sloper-Mould, K. E. & Hicke, L. Monoubiquitin carries a novel internalization signal that is appended to activated receptors. EMBO J.19, 187–198 (2000). Shows, for the first time, that monoubiquitylation serves as an endocytic signal. ArticleCASPubMedPubMed Central Google Scholar
Huang, K. et al. A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is essential for Caenorhabditis elegans embryogenesis. Gene252, 137–145 (2000). ArticleCASPubMed Google Scholar
Astin, J. W., O'Neil, N. J. & Kuwabara, P. E. Nucleotide excision repair and the degradation of RNA pol II by the Caenorhabditis elegans XPA and Rsp5 orthologues, RAD-3 and WWP-1. DNA Repair (Amst.)7, 267–280 (2008). ArticleCAS Google Scholar
Shaye, D. D. & Greenwald, I. LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans. Development132, 5081–5092 (2005). ArticleCASPubMed Google Scholar
Ing, B. et al. Regulation of Commissureless by the ubiquitin ligase DNedd4 is required for neuromuscular synaptogenesis in Drosophila melanogaster. Mol. Cell. Biol.27, 481–496 (2007). ArticleCASPubMed Google Scholar
Sakata, T. et al. Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation. Curr. Biol.14, 2228–2236 (2004). ArticleCASPubMed Google Scholar
Wilkin, M. B. et al. Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr. Biol.14, 2237–2244 (2004). ArticleCASPubMed Google Scholar
Podos, S. D., Hanson, K. K., Wang, Y. C. & Ferguson, E. L. The DSmurf ubiquitin–protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis. Dev. Cell1, 567–578 (2001). ArticleCASPubMed Google Scholar
Liang, Y. Y. et al. dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development. J. Biol. Chem.278, 26307–26310 (2003). ArticleCASPubMed Google Scholar
Cao, X. R. et al. Nedd4 controls animal growth by regulating IGF-1 signaling. Sci. Signal.1, ra5 (2008). Identifies NEDD4 as a positive growth regulator of mammalian cells and tissues. ArticleCASPubMedPubMed Central Google Scholar
Fouladkou, F. et al. The ubiquitin ligase Nedd4–1 is dispensable for the regulation of PTEN stability and localization. Proc. Natl Acad. Sci. USA105, 8585–8590 (2008). ArticleCASPubMedPubMed Central Google Scholar
Zhu, H., Kavsak, P., Abdollah, S., Wrana, J. L. & Thomsen, G. H. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature400, 687–693 (1999). ArticleCASPubMed Google Scholar
Yamashita, M. et al. Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell121, 101–113 (2005). ArticleCASPubMedPubMed Central Google Scholar
Ozdamar, B. et al. Regulation of the polarity protein Par6 by TGFβ receptors controls epithelial cell plasticity. Science307, 1603–1609 (2005). Describes the important role of SMURF1 in the degradation of RhoA and the regulation of the epithelial-to-mesenchymal transition. ArticleCASPubMed Google Scholar
Zhang, Y., Chang, C., Gehling, D. J., Hemmati-Brivanlou, A. & Derynck, R. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc. Natl Acad. Sci. USA98, 974–979 (2001). ArticleCASPubMedPubMed Central Google Scholar
Lin, X., Liang, M. & Feng, X. H. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-β signaling. J. Biol. Chem.275, 36818–36822 (2000). ArticleCASPubMed Google Scholar
Kavsak, P. et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGFβ receptor for degradation. Mol. Cell6, 1365–1375 (2000). ArticleCASPubMed Google Scholar
Bonni, S. et al. TGF-β induces assembly of a Smad2–Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nature Cell Biol.3, 587–595 (2001). ArticleCASPubMed Google Scholar
Gao, M. et al. Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Science306, 271–275 (2004). ArticleCASPubMed Google Scholar
Chang, L. et al. The E3 ubiquitin ligase Itch couples JNK activation to TNFα-induced cell death by inducing c-FLIPL turnover. Cell124, 601–613 (2006). ArticleCASPubMed Google Scholar
Rossi, M. et al. The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc. Natl Acad. Sci. USA103, 12753–12758 (2006). ArticleCASPubMedPubMed Central Google Scholar
Kamynina, E., Debonneville, C., Bens, M., Vandewalle, A. & Staub, O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J.15, 204–214 (2001). ArticleCASPubMed Google Scholar
Harvey, K. F., Dinudom, A., Cook, D. I. & Kumar, S. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J. Biol. Chem.276, 8597–8601 (2001). ArticleCASPubMed Google Scholar
Lu, C., Pribanic, S., Debonneville, A., Jiang, C. & Rotin, D. The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. Traffic8, 1246–1264 (2007). ArticleCASPubMed Google Scholar
Pak, Y., Glowacka, W. K., Bruce, M. C., Pham, N. & Rotin, D. Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination. J. Cell Biol.175, 631–645 (2006). ArticleCASPubMedPubMed Central Google Scholar
Saksena, S., Sun, J., Chu, T. & Emr, S. D. ESCRTing proteins in the endocytic pathway. Trends Biochem. Sci.32, 561–573 (2007). ArticleCASPubMed Google Scholar
Morita, E. & Sundquist, W. I. Retrovirus budding. Annu. Rev. Cell Dev. Biol.20, 395–425 (2004). ArticleCASPubMed Google Scholar
Okumura, A., Pitha, P. M. & Harty, R. N. ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proc. Natl Acad. Sci. USA105, 3974–3979 (2008). ArticleCASPubMedPubMed Central Google Scholar
Malakhova, O. A. & Zhang, D. E. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response. J. Biol. Chem.283, 8783–8787 (2008). References 57 and 58 provide the first demonstration of inhibition of HECT ligase by a ubiquitin-like protein. ArticleCASPubMedPubMed Central 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). ArticleCAS Google Scholar
Perry, W. L. et al. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a_18H_ mice. Nature Genet.18, 143–146 (1998). ArticleCASPubMed Google Scholar
Fang, D. et al. Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation. Nature Immunol.3, 281–287 (2002). Reference 62 and 63 found that loss of the HECT E3 ligase ITCH causes immune defects. ArticleCAS Google Scholar
Venuprasad, K. et al. Convergence of Itch-induced ubiquitination with MEKK1–JNK signaling in Th2 tolerance and airway inflammation. J. Clin. Invest.116, 1117–1126 (2006). ArticleCASPubMedPubMed Central Google Scholar
Heissmeyer, V. et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nature Immunol.5, 255–265 (2004). ArticleCAS Google Scholar
Chen, C. et al. Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. Oncogene26, 2386–2394 (2007). ArticleCASPubMed Google Scholar
Chen, C., Zhou, Z., Ross, J. S., Zhou, W. & Dong, J. T. The amplified WWP1 gene is a potential molecular target in breast cancer. Int. J. Cancer121, 80–87 (2007). ArticleCASPubMed Google Scholar
Chen, C. et al. Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J. Biol. Chem.280, 41553–41561 (2005). ArticleCASPubMed Google Scholar
Laine, A. & Ronai, Z. Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. Oncogene26, 1477–1483 (2007). ArticleCASPubMed Google Scholar
Foot, N. J. et al. Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2. Blood112, 4268–4275 (2008). Provides an example of how specific mammalian adaptor proteins can mediate the regulation of a substrate by a HECT E3. ArticleCASPubMed Google Scholar
Lifton, R. P., Gharavi, A. G. & Geller, D. S. Molecular mechanisms of human hypertension. Cell104, 545–556 (2001). ArticleCASPubMed Google Scholar
Shi, P. P. et al. Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4–2. Am. J. Physiol. Renal Physiol.295, F462–F470 (2008). ArticleCASPubMedPubMed Central Google Scholar
Pradervand, S. et al. A mouse model for Liddle's syndrome. J. Am. Soc. Nephrol.10, 2527–2533 (1999). CASPubMed Google Scholar
Miyazaki, K. et al. A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity. Biochem. Biophys. Res. Commun.308, 106–113 (2003). ArticleCASPubMed Google Scholar
Li, Y. et al. A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner. Oncogene27, 3700–3709 (2008). ArticleCASPubMed Google Scholar
Miyazaki, K. et al. NEDL1, a novel ubiquitin–protein isopeptide ligase for dishevelled-1, targets mutant superoxide dismutase-1. J. Biol. Chem.279, 11327–11335 (2004). ArticleCASPubMed Google Scholar
Garcia-Gonzalo, F. R., Bartrons, R., Ventura, F. & Rosa, J. L. Requirement of phosphatidylinositol-4,5-bisphosphate for HERC1-mediated guanine nucleotide release from ARF proteins. FEBS Lett.579, 343–348 (2005). ArticleCASPubMed Google Scholar
Chong-Kopera, H. et al. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J. Biol. Chem.281, 8313–8316 (2006). ArticleCASPubMed Google Scholar
Lehman, A. L. et al. A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice. Proc. Natl Acad. Sci. USA95, 9436–9441 (1998). ArticleCASPubMedPubMed Central Google Scholar
Sturm, R. A. et al. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am. J. Hum. Genet.82, 424–431 (2008). ArticleCASPubMedPubMed Central Google Scholar
Eiberg, H. et al. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum. Genet.123, 177–187 (2008). References 80 and 81 were the first to implicate HERC2 in the determination of eye colour. ArticleCASPubMed Google Scholar
Hochrainer, K., Kroismayr, R., Baranyi, U., Binder, B. R. & Lipp, J. Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B. Cell. Mol. Life Sci.65, 2105–2117 (2008). ArticleCASPubMed Google Scholar
Cruz, C., Ventura, F., Bartrons, R. & Rosa, J. L. HERC3 binding to and regulation by ubiquitin. FEBS Lett.488, 74–80 (2001). ArticleCASPubMed Google Scholar
Rodriguez, C. I. & Stewart, C. L. Disruption of the ubiquitin ligase HERC4 causes defects in spermatozoon maturation and impaired fertility. Dev. Biol.312, 501–508 (2007). ArticleCASPubMed Google Scholar
Kroismayr, R. et al. HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells. J. Cell Sci.117, 4749–4756 (2004). ArticleCASPubMed Google Scholar
Dastur, A., Beaudenon, S., Kelley, M., Krug, R. M. & Huibregtse, J. M. Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells. J. Biol. Chem.281, 4334–4338 (2006). ArticleCASPubMed Google Scholar
Wong, J. J., Pung, Y. F., Sze, N. S. & Chin, K. C. HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc. Natl Acad. Sci. USA103, 10735–10740 (2006). ArticleCASPubMedPubMed Central Google Scholar
Yoshida, M. et al. Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its inhibitor, Paip2. EMBO J.25, 1934–1944 (2006). ArticleCASPubMedPubMed Central Google Scholar
Henderson, M. J. et al. EDD mediates DNA damage-induced activation of CHK2. J. Biol. Chem.281, 39990–40000 (2006). ArticleCASPubMed Google Scholar
Ohshima, R. et al. Putative tumor suppressor EDD interacts with and up-regulates APC. Genes Cells12, 1339–1345 (2007). ArticleCASPubMed Google Scholar
Saunders, D. N. et al. Edd, the murine hyperplastic disc gene, is essential for yolk sac vascularization and chorioallantoic fusion. Mol. Cell. Biol.24, 7225–7234 (2004). ArticleCASPubMedPubMed Central Google Scholar
Chen, D. et al. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell121, 1071–1083 (2005). ArticleCASPubMed Google Scholar
Zhong, Q., Gao, W., Du, F. & Wang, X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell121, 1085–1095 (2005). ArticleCASPubMed Google Scholar
Adhikary, S. et al. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell123, 409–421 (2005). ArticleCASPubMed Google Scholar
Zhao, X. et al. The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nature Cell Biol.10, 643–653 (2008). This important work identified NMYC as the substrate for HUWE1 and thus the control of HUWE1 in neuronal differentiation. ArticleCASPubMed Google Scholar
Froyen, G. et al. Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am. J. Hum. Genet.82, 432–443 (2008). ArticleCASPubMedPubMed Central Google Scholar
Vu, T. H. & Hoffman, A. R. Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain. Nature Genet.17, 12–13 (1997). ArticleCASPubMed Google Scholar
Rougeulle, C., Glatt, H. & Lalande, M. The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain. Nature Genet.17, 14–15 (1997). References 99 and 100 identifiedE6APas an imprinted gene and found that mutations in theE6APgene cause Angelman syndrome, a neurodevelopmental disorder. ArticleCASPubMed Google Scholar
Kishino, T., Lalande, M. & Wagstaff, J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature Genet.15, 70–73 (1997). ArticleCASPubMed Google Scholar
Jiang, Y. H. et al. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron21, 799–811 (1998). ArticleCASPubMed Google Scholar
Colas, D., Wagstaff, J., Fort, P., Salvert, D. & Sarda, N. Sleep disturbances in Ube3a maternal-deficient mice modeling Angelman syndrome. Neurobiol. Dis.20, 471–478 (2005). ArticleCASPubMed 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). This seminal work identified E6AP as the E3 ligase for the tumour suppressor p53 in HPV-infected cells. Such an infection can lead to cervical cancer. ArticleCASPubMed Google Scholar
Martin, P., Martin, A. & Shearn, A. Studies of l(3)_c_43_hs_1 a polyphasic, temperature-sensitive mutant of Drosophila melanogaster with a variety of imaginal disc defects. Dev. Biol.55, 213–232 (1977). ArticleCASPubMed Google Scholar
Lee, J. D., Amanai, K., Shearn, A. & Treisman, J. E. The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms. Development129, 5697–5706 (2002). ArticleCASPubMed Google Scholar
Clancy, J. L. et al. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene22, 5070–5081 (2003). ArticleCASPubMed Google Scholar
Fuja, T. J., Lin, F., Osann, K. E. & Bryant, P. J. Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 ε, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer Res.64, 942–951 (2004). ArticleCASPubMed Google Scholar
Anglesio, M. S. et al. Differential expression of a novel ankyrin containing E3 ubiquitin–protein ligase, Hace1, in sporadic Wilms' tumor versus normal kidney. Hum. Mol. Genet.13, 2061–2074 (2004). ArticleCASPubMed Google Scholar
Hibi, K. et al. Aberrant methylation of the HACE1 gene is frequently detected in advanced colorectal cancer. Anticancer Res.28, 1581–1584 (2008). CASPubMed Google Scholar
Zhang, L. et al. The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers. Nature Med.13, 1060–1069 (2007). Provides directin vivoevidence using knockout mice for the function of HACE1 as a tumour suppressor. ArticleCASPubMed Google Scholar
Zohn, I. E., Anderson, K. V. & Niswander, L. The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure. Dev. Biol.306, 208–221 (2007). ArticleCASPubMedPubMed Central Google Scholar
Crosas, B. et al. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell127, 1401–1413 (2006). ArticleCASPubMed Google Scholar
Brooks, W. S. et al. G2E3 is a dual function ubiquitin ligase required for early embryonic development. J. Biol. Chem.283, 22304–22315 (2008). ArticleCASPubMedPubMed Central Google Scholar
Debonneville, C. et al. Phosphorylation of Nedd4–2 by Sgk1 regulates epithelial Na+ channel cell surface expression. EMBO J.20, 7052–7059 (2001). ArticleCASPubMedPubMed Central Google Scholar
Snyder, P. M., Olson, D. R. & Thomas, B. C. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. J. Biol. Chem.277, 5–8 (2002). ArticleCASPubMed Google Scholar
Oberst, A. et al. The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proc. Natl Acad. Sci. USA104, 11280–11285 (2007). ArticleCASPubMedPubMed 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). ArticleCASPubMedPubMed Central Google Scholar
Bruce, M. C. et al. Regulation of Nedd4–2 self-ubiquitination and stability by a PY motif located within its HECT-domain. Biochem. J.415, 155–163 (2008). ArticleCASPubMed Google Scholar
Lu, K. et al. Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nature Cell Biol.10, 994–1002 (2008). ArticleCASPubMed Google Scholar
Spana, E. P. & Doe, C. Q. Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron17, 21–26 (1996). ArticleCASPubMed Google Scholar
McGill, M. A. & McGlade, C. J. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J. Biol. Chem.278, 23196–23203 (2003). ArticleCASPubMed Google Scholar
Kee, Y., Lyon, N. & Huibregtse, J. M. The Rsp5 ubiquitin ligase is coupled to and antagonized by the Ubp2 deubiquitinating enzyme. EMBO J.24, 2414–2424 (2005). ArticleCASPubMedPubMed Central Google Scholar
Liu, X. F. & Culotta, V. C. Post-translation control of Nramp metal transport in yeast. Role of metal ions and the BSD2 gene. J. Biol. Chem.274, 4863–4868 (1999). ArticleCASPubMed Google Scholar
Hettema, E. H., Valdez-Taubas, J. & Pelham, H. R. Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins. EMBO J.23, 1279–1288 (2004). ArticleCASPubMedPubMed Central Google Scholar
Liu, X. F., Supek, F., Nelson, N. & Culotta, V. C. Negative control of heavy metal uptake by the Saccharomyces cerevisiae BSD2 gene. J. Biol. Chem.272, 11763–11769 (1997). ArticleCASPubMed Google Scholar
Stimpson, H. E., Lewis, M. J. & Pelham, H. R. Transferrin receptor-like proteins control the degradation of a yeast metal transporter. EMBO J.25, 662–672 (2006). ArticleCASPubMedPubMed Central Google Scholar
Shearwin-Whyatt, L., Dalton, H. E., Foot, N. & Kumar, S. Regulation of functional diversity within the Nedd4 family by accessory and adaptor proteins. Bioessays28, 617–628 (2006). ArticleCASPubMed Google Scholar
Oliver, P. M. et al. Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Immunity25, 929–940 (2006). ArticleCASPubMedPubMed Central Google Scholar
Putz, U. et al. Nedd4-family interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4-family proteins. J. Biol. Chem.283, 32621–32627 (2008). ArticleCASPubMed Google Scholar
Nikko, E., Sullivan, J. A. & Pelham, H. R. Arrestin-like proteins mediate ubiquitination and endocytosis of the yeast metal transporter Smf1. EMBO Rep.9, 1216–1221 (2008). ArticleCASPubMedPubMed Central Google Scholar
Lin, C. H., Macgurn, J. A., Chu, T., Stefan, C. J. & Emr, S. D. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. Cell135, 714–725 (2008). References 132 and 133 provide evidence that arrestin-like proteins act as adaptors for Rsp5 to regulate protein turnover and endocytosis. ArticleCASPubMed Google Scholar
Leon, S., Erpapazoglou, Z. & Haguenauer-Tsapis, R. Ear1p and Ssh4p are new adaptors of the ubiquitin ligase Rsp5p for cargo ubiquitylation and sorting at multivesicular bodies. Mol. Biol. Cell19, 2379–2388 (2008). ArticleCASPubMedPubMed Central Google Scholar
Gupta, R. et al. Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeast. Mol. Syst. Biol.3, 116 (2007). ArticleCASPubMedPubMed Central Google Scholar
Yen, H. C., Xu, Q., Chou, D. M., Zhao, Z. & Elledge, S. J. Global protein stability profiling in mammalian cells. Science322, 918–923 (2008). Describes a novel proteomic approach to identify substrates for E3 ligasesin vivo . ArticleCASPubMed Google Scholar
Tokunaga, F. et al. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nature Cell Biol.11, 123–132 (2009). ArticleCASPubMed Google Scholar
Rahighi, S. et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell136, 1098–1109 (2009). ArticleCASPubMed Google Scholar