This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
WSB1, as an E3 ligase, restrains myocardial ischemia–reperfusion injury by activating β-catenin signaling via promoting GSK3β ubiquitination
Molecular Medicine Open Access 23 February 2024
-
Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease
Scientific Reports Open Access 20 October 2022
-
Concept and application of circulating proteasomes
Experimental & Molecular Medicine Open Access 27 October 2021
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Schoenheimer, R. The Dynamic State of Body Constituents (Harvard University Press, Cambridge, Massachusetts, 1942).
Schimke, R.T. & Doyle, D. Control of enzyme levels in animal tissues. Annu. Rev. Biochem. 39, 929–979 (1971).
Haider, M. & Segal, H.L. Some characteristics of the alanine aminotransferase- and arginase-inactivating system of lysosomes. Arch. Biochem. Biophys. 148, 228–237 (1972).
Hershko, A. & Tomkins, G.M. Studies on the degradation of tyrosine aminotransferase in hepatoma cells in culture. Influence of the composition of the medium and adenosine triphosphate dependence. J. Biol. Chem. 246, 710–714 (1971).
Simpson, M.V. The release of labeled amino acids from proteins in liver slices. J. Biol. Chem. 201, 143–154 (1953).
Hershko, A. & Ciechanover, A. Mechanisms of intracellular protein breakdown. Annu. Rev. Biochem. 51, 335–364 (1982).
Etlinger, J.D. & Goldberg, A.L. A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc. Natl. Acad. Sci. USA. 74, 54–58 (1977).
Ciechanover, A., Hod, Y. & Hershko, A. a heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem. Biophys. Res. Commun. 81, 1100–1105 (1978).
Wilkinson, K.D., Urban, M.K. & Haas, A.L. Ubiquitin is the ATP-dependent proteolysis factor of rabbit reticulocytes. J. Biol. Chem. 255, 7529–7532 (1980).
Goldstein, G. et al. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc. Natl. Acad. Sci. USA. 72, 11–15 (1975).
Goldknopf, I.L. & Busch, H. Isopeptide linkage between nonhistone and histone A polypeptides of chromosomal conjugate protein A24. Proc. Natl. Acad. Sci. USA. 74, 864–868 (1977).
Ciechanover, A., Heller, H., Elias, S., Haas, A. L. & Hershko, A. ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. Proc. Natl. Acad. Sci. USA. 77, 1365–1368 (1980).
Hershko, A., Ciechanover, A, Heller, H., Haas, A. L. & Rose, I. A. Proposed role of ATP in protein breakdown: conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc. Natl. Acad. Sci. USA. 77, 1783–1786 (1980).
Lam, Y.A., Xu, W., DeMartino, G.N. & Cohen, R.E. Editing of ubiquitin conjugates by an isopeptidase of the 26S proteasome. Nature 385, 737–740 (1997).
Hershko, A. & Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem. 67, 425–479 (1998).
Hershko, A., Heller, H., Elias, S. & Ciechanover, A. Components of ubiquitin-protein ligase system: resolution, affinity purification and role in protein breakdown. J. Biol. Chem. 258, 8206–8214 (1983).
Hershko, A., Heller, A., Eytan, E. & Reiss, Y. The protein binding site of the ubiquitin-protein ligase system. J. Biol. Chem. 261, 11992–11999 (1986).
Hough, R., Pratt, G. & Rechsteiner, M. Ubiquitin-lysozyme conjugates. Identification and characterization of an ATP-dependent protease from rabbit reticulocyte lysates. J. Biol. Chem. 261, 2400–2408 (1986).
Hershko, A. Lessons from the discovery of the ubiquitin system. Trends Biochem. Sci. 21, 445–449 (1996).
Hershko, A., Heller, H., Ganoth, D. & Ciechanover, A. in Protein Turnover and Lysosome Function (eds. Segal, H.L. & Doyle, D.J.) 149–169 (Academic Press, New York, 1978).
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).
Wilkinson, K.D., Urban, M.K. & Haas, A.L. Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J. Biol. Chem. 255, 7529–7532 (1980).
Hershko, A. & Heller, H. Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Common. 128, 1079–1086 (1985).
Chau, V. et al. A multiubiquitin chain is confined to specific Lysine in a targeted short-lived protein. Science 243, 1576–1583 (1989).
Lipmann, F, Gevers, W., Kleinkauf, H. & Roskoski, R. Jr. Polypeptide synthesis on protein templates: The enzymatic synthesis of gramicidin S and tyrocidine. Adv. Enzymol. Relat. Areas Mol. Biol. 35, 1–34 (1971).
Ciechanover, A., Elias, S., Heller, H. & Hershko, A. “Covalent affinity” purification of ubiquitin activating enzyme. J. Biol. Chem. 257, 2537–2542 (1982).
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).
Finley, D., Ciechanover, A. & Varshavsky, A. . Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell 37, 43–55 (1984).
Ciechanover, A., Finley D. & Varshavsky, A. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell 37, 57–66 (1984).
Ferber, S. & Ciechanover, A. Transfer RNA is required for conjugation of ubiquitin to selective substrates of the ubiquitin- and ATP-dependent proteolytic system. J. Biol. Chem. 261, 3128–3134 (1986).
Ferber, S. & Ciechanover, A. Role of arginine-tRNA in protein degradation by the ubiquitin pathway. Nature 326, 808–811 (1987).
Varshavsky, A. The N-end rule pathway of protein degradation. Genes Cells 2, 13–28 (1997).
Hershko, A., Heller, H., Eytan, E., Kaklij, G. & Rose, I.A. Role of α-amino group of protein in ubiquitin-mediated protein breakdown. Proc. Natl. Acad. Sci. USA 81, 7021–7025 (1984).
Mayer, A. Siegel, N.R., Schwartz, A.L. & Ciechanover, A. Degradation of proteins with acetylated amino termini by the ubiquitin system. Science 244, 1480–1483 (1989).
Scheffner, M., Werness, B.A., Huibregtse, J.M., Levine, A.J. & Howley, P.M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129–1136 (1990).
Glotzer, M., Murray, A.W. & Kirschner M.W. Cyclin is degraded by the ubiquitin pathway. Nature 349, 132–138 (1991).
Hershko, A., Ganoth, D., Pehrson, J., Palazzo, R.E., & Cohen, L.H. . Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. J. Biol. Chem. 266, 16376–16379 (1991).
Ciechanover, A. et al. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc. Natl. Acad. Sci. USA 88, 139–143 (1991).
Ciechanover, A., Orian, A. & Schwartz, A.L.. Ubiquitin-mediated proteolysis: Biological regulation via destruction. BioEssays 22, 442–451 (2000).
Yaron, A. et al. Inhibition of NF-κB cellular function via specific targeting of the IκBα-ubiquitin ligase. EMBO J. 16, 6486–6494 (1997).
Butz, K., Denk, C., Ullmann, A., Scheffner, M. & Hoppe-Seyler, F. Induction of apoptosis in human papillomavirus positive cancer cells by peptide aptamers targeting the viral E6 oncoprotein. Proc. Natl. Acad. Sci. USA 97, 6693–6697 (2000).
Finley, D., Özkaynak, E. & Varshavsky, A. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. Cell 48, 1035–1046 (1987).
Jentsch, S., McGrath, J.P. & Varshavsky, A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329, 131–134 (1987).
Goebl, M.G. et al. The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science 241, 1331–1335 (1988).
Finley, D., Bartel, B. & Varshavsky, A. The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature 338, 394–401 (1989).
Bachmair, A., Finley, D. & Varshavsky, A. In vivo half-life of a protein is a function of its amino-terminal residue. Science 234, 179–186 (1986).
Varshavsky, A. Ubiquitin fusion technique and its descendants. Meth. Enzymol. 327, 578–593 (2000).
Varshavsky, A. The N-end rule: functions, mysteries, uses. Proc. Natl. Acad. Sci. USA 93, 12142–12149 (1996).
Johnson, E. S., Ma, P. C., Ota, I. M. & Varshavsky, A. A proteolytic pathway that recognizes ubiquitin as a degradation signal. J. Biol. Chem. 270, 17442–17456 (1995).
Suzuki, T. & Varshavsky, A. Degradation signals in the lysine-asparagine sequence space. EMBO J. 18, 6017–6026 (1999).
Varshavsky, A. The ubiquitin system. Trends Biochem. Sci. 22, 383–387 (1997).
Xie, Y. & Varshavsky, A. Physical association of ubiquitin ligases and the 26S proteasome. Proc. Natl. Acad. Sci. USA 97, 2497–2502 (2000).
Johnson, E.S., Gonda, D.K. & Varshavsky, A. Cis-trans recognition and subunit-specific degradation of short-lived proteins. Nature 346, 287–291 (1990).
Kwon, Y.T. et al. Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway. Mol. Cell. Biol. 20, 4135–4148 (2000).
Davydov, I.V. & Varshavsky, A. RGS4 is arginylated and degraded by the N-end rule pathway in vitro. J. Biol. Chem. 275, 22931–22941 (2000).
Byrd, C., Turner, G.C. & Varshavsky, A. The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor. EMBO J. 17, 269–277 (1998).
Turner, G., Du, F. & Varshavsky, A. Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway. Nature 405, 579–582 (2000).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hershko, A., Ciechanover, A. & Varshavsky, A. The ubiquitin system. Nat Med 6, 1073–1081 (2000). https://doi.org/10.1038/80384
Issue Date:
DOI: https://doi.org/10.1038/80384
This article is cited by
-
WSB1, as an E3 ligase, restrains myocardial ischemia–reperfusion injury by activating β-catenin signaling via promoting GSK3β ubiquitination
Molecular Medicine (2024)
-
O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation
Oncogene (2024)
-
Validation of catalytic site residues of Ubiquitin Specific Protease 2 (USP2) by molecular dynamic simulation and novel kinetics assay for rational drug design
Molecular Diversity (2023)
-
Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease
Scientific Reports (2022)
-
TRIM-away via Gln/C-degrons
Nature Chemical Biology (2022)