Schoenheimer, R. The Dynamic State of Body Constituents (Harvard University Press, Cambridge, Massachusetts, 1942). Google Scholar
Schimke, R.T. & Doyle, D. Control of enzyme levels in animal tissues. Annu. Rev. Biochem.39, 929–979 (1971). Article Google Scholar
Haider, M. & Segal, H.L. Some characteristics of the alanine aminotransferase- and arginase-inactivating system of lysosomes. Arch. Biochem. Biophys.148, 228–237 (1972). ArticleCAS Google Scholar
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). CAS Google Scholar
Simpson, M.V. The release of labeled amino acids from proteins in liver slices. J. Biol. Chem.201, 143–154 (1953). CAS Google Scholar
Hershko, A. & Ciechanover, A. Mechanisms of intracellular protein breakdown. Annu. Rev. Biochem.51, 335–364 (1982). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
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). Article Google Scholar
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). CAS Google Scholar
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). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
Lam, Y.A., Xu, W., DeMartino, G.N. & Cohen, R.E. Editing of ubiquitin conjugates by an isopeptidase of the 26S proteasome. Nature385, 737–740 (1997). ArticleCAS Google Scholar
Hershko, A. & Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem.67, 425–479 (1998). ArticleCAS Google Scholar
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). CAS Google Scholar
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). CASPubMed Google Scholar
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). CAS Google Scholar
Hershko, A. Lessons from the discovery of the ubiquitin system. Trends Biochem. Sci.21, 445–449 (1996). ArticleCAS Google Scholar
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). Book 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). CAS Google Scholar
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). CAS Google Scholar
Hershko, A. & Heller, H. Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Common.128, 1079–1086 (1985). ArticleCAS Google Scholar
Chau, V. et al. A multiubiquitin chain is confined to specific Lysine in a targeted short-lived protein. Science243, 1576–1583 (1989). ArticleCAS Google Scholar
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). CASPubMed Google Scholar
Ciechanover, A., Elias, S., Heller, H. & Hershko, A. “Covalent affinity” purification of ubiquitin activating enzyme. J. Biol. Chem.257, 2537–2542 (1982). 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). CAS Google Scholar
Finley, D., Ciechanover, A. & Varshavsky, A. . Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell37, 43–55 (1984). ArticleCAS Google Scholar
Ciechanover, A., Finley D. & Varshavsky, A. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell37, 57–66 (1984). ArticleCAS Google Scholar
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). CASPubMed Google Scholar
Ferber, S. & Ciechanover, A. Role of arginine-tRNA in protein degradation by the ubiquitin pathway. Nature326, 808–811 (1987). ArticleCAS Google Scholar
Varshavsky, A. The N-end rule pathway of protein degradation. Genes Cells2, 13–28 (1997). ArticleCAS Google Scholar
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. USA81, 7021–7025 (1984). ArticleCAS Google Scholar
Mayer, A. Siegel, N.R., Schwartz, A.L. & Ciechanover, A. Degradation of proteins with acetylated amino termini by the ubiquitin system. Science244, 1480–1483 (1989). ArticleCAS Google Scholar
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. Cell63, 1129–1136 (1990). ArticleCAS Google Scholar
Glotzer, M., Murray, A.W. & Kirschner M.W. Cyclin is degraded by the ubiquitin pathway. Nature349, 132–138 (1991). ArticleCAS Google Scholar
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). CASPubMed Google Scholar
Ciechanover, A. et al. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc. Natl. Acad. Sci. USA88, 139–143 (1991). ArticleCAS Google Scholar
Ciechanover, A., Orian, A. & Schwartz, A.L.. Ubiquitin-mediated proteolysis: Biological regulation via destruction. BioEssays22, 442–451 (2000). ArticleCAS Google Scholar
Yaron, A. et al. Inhibition of NF-κB cellular function via specific targeting of the IκBα-ubiquitin ligase. EMBO J.16, 6486–6494 (1997). ArticleCAS Google Scholar
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. USA97, 6693–6697 (2000). ArticleCAS Google Scholar
Finley, D., Özkaynak, E. & Varshavsky, A. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. Cell48, 1035–1046 (1987). ArticleCAS Google Scholar
Jentsch, S., McGrath, J.P. & Varshavsky, A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature329, 131–134 (1987). ArticleCAS Google Scholar
Goebl, M.G. et al. The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science241, 1331–1335 (1988). ArticleCAS Google Scholar
Finley, D., Bartel, B. & Varshavsky, A. The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature338, 394–401 (1989). ArticleCAS Google Scholar
Bachmair, A., Finley, D. & Varshavsky, A. In vivo half-life of a protein is a function of its amino-terminal residue. Science234, 179–186 (1986). ArticleCAS Google Scholar
Varshavsky, A. Ubiquitin fusion technique and its descendants. Meth. Enzymol.327, 578–593 (2000). ArticleCAS Google Scholar
Varshavsky, A. The N-end rule: functions, mysteries, uses. Proc. Natl. Acad. Sci. USA93, 12142–12149 (1996). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
Suzuki, T. & Varshavsky, A. Degradation signals in the lysine-asparagine sequence space. EMBO J.18, 6017–6026 (1999). ArticleCAS Google Scholar
Varshavsky, A. The ubiquitin system. Trends Biochem. Sci.22, 383–387 (1997). ArticleCAS Google Scholar
Xie, Y. & Varshavsky, A. Physical association of ubiquitin ligases and the 26S proteasome. Proc. Natl. Acad. Sci. USA97, 2497–2502 (2000). ArticleCAS Google Scholar
Johnson, E.S., Gonda, D.K. & Varshavsky, A. Cis-trans recognition and subunit-specific degradation of short-lived proteins. Nature346, 287–291 (1990). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
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). ArticleCAS Google Scholar
Turner, G., Du, F. & Varshavsky, A. Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway. Nature405, 579–582 (2000). ArticleCAS Google Scholar