Abstract
Ubiquitin has been suggested to play a key role in a wide variety of essential cellular functions ranging from differential regulation of gene expression to protein degradation. Recent studies on natural and synthetic ubiquitin gene fusions have led to important discoveries concerning novel functions for the ubiquitin system in cells, mechanisms of proteolytic processing, and the development of a ubiquitin fusion technology for augmenting the expression of heterologous gene products in bacteria and yeast. Furthermore, studies involving site-directed mutagenesis and two-dimensional NMR have proven ubiquitin to be an excellent model for protein engineering and have led to important discoveries concerning its mechanism of action in ATP-dependent proteolysis. Finally, the recent identification and characterization of ubiquitin carboxyl extension proteins as ribosomal proteins has opened up an even newer area of ubiquitin-related research and has helped to explain the mechanisms involved in increasing the expression of heterologous gene products made as ubiquitin fusions.
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References
Finley, D. and Varshavsky, A. 1985. The ubiquitin system: Functions and mechanisms. Trends Biochem. Sci. 10: 343–347.
Hershko, A. and Ciechanover, A. 1986. The ubiquitin pathway for the degradation of intracellular proteins. Proc. Nucleic Acid Res. Mol. Biol. 33: 19–56.
Rechsteiner, M. 1987. Ubiquitin-mediated pathways for intracellular proteolysis. Ann. Rev. Cell Biol. 3: 1–30.
Hershko, A. 1988. Ubiquitin-mediated protein degradation. J. Biol. Chem. 263: 15237–15240.
Ozkaynak, E., Finley, D., Solomon, M-J. and Varshavsky, A. 1987. The yeast ubiquitin genes: A family of natural gene fusions. EMBO J. 6: 1429–1439.
Muller-Taubenberger, A., Westphal, M., Jaeger, E., Noegel, A. and Gerisch, G. 1988. Complete cDNA sequence of a distyostelium ubiquitin with a carboxy-terminal tail and identification of the protein using an anti-peptide antibody. FEBS 229: 273–278.
Ohmachi, T., Giorda, R., Shaw, D.R. and Ennis, H.L. 1989. Molecular organization of developmentally regulated Dictyostelium discoideum ubiquitin cDNAs. Biochemistry 28: 5226–5231.
Gausing, K. and Barkardottir, R. 1986. Structure and expression of ubiquitin genes in higher plants. Eur. J. Biochem. 158: 57–62.
Dworkin-Rastl, E., Shrutkowski, A. and Dworkin, M.B. 1984. Multiple ubiquitin mRNAs during Xenopus laevis development contain tandem repeats of the 76 amino acid coding sequence. Cell 39: 321–325.
Bond, U. and Schlesinger, M.J. 1985. Ubiquitin is a heat shock protein in chicken embryo fibroblasts. Mol. Cell Biol. 5: 949–959.
Arribas, C., Sampedro, J. and Izquierdo, M. 1986. The ubiquitin genes in D. melanogaster: Transcription and polymorphism. Biochem-Biophys. Acta 868: 119–127.
Swindle, J., Ajioka, J., Eisen, H., Sanwal, B., Jacquemot, C., Browder, Z. and Buck, G. 1988. The genomic organization and transcription of the ubiquitin genes of Trypanosoma cruzi. EMBO J. 7: 1121–1127.
Wiborg, O., Pedersen, M.S., Wind, A., Berglund, L.E., Marcker, K.A. and Vuust, J. 1985. The human ubiquitin gene family: Some genes contain multiple directly repeated ubiquitin coding sequences. EMBO J. 4: 755–759.
Baker, R.T. and Board, P.G. 1987. The human ubiquitin gene family: Structure of a gene and pseudogenes from the UbB subfamily. Nucleic Acids Res. 15: 443–463.
Lund, P.K., Moats-Staats, B.M., Simmons, J.G., Hoyt, E., D'Ercole, A.J., Martin, F. and Van Wyk, J.J. 1985. Nucleotide sequence analysis of a DNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor. J. Biol. Chem. 260: 7609–7613.
Salveson, G., Lloyd, C. and Farley, D. 1987. cDNa encoding a human homolog of yeast ubiquitin 1. Nucleic Acids Res. 15: 5485–5486.
St. John, T., Gallatin, W.M., Siegelman, M., Smith, H.T., Fried, V.A. and Weissman, I.L. 1986 Expression cloning of a lymphocyte homing receptor cDNA. Ubiquitin is the reactive species. Science 231: 845–850.Ch.
Wool, I.G. 1979. The structure and function of eukaryotic ribosomes. Ann. Rev. Biochem. 48: 719–754.
Long, C.W., Henderson, L.E. and Oroszlan, S. 1980. Isolation and characterization of low molecular weight DNA-binding proteins from retroviruses. Virology 104: 491–496.
Berg, J.M. 1986. Potential metal-binding domains in nucleic acid binding proteins. Science 232: 485–487.
Lee, M.S., Gippert, G.P., Soman, K.V., Case, D.A. and Wright, P.E. 1989. Three-dimensional structure solution of a single zinc finger DNA binding domain. Science 245: 635–637.
Miller, J., McLachlan, A.D. and Klug, A. 1985. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus ocytes. EMBO J. 4: 1609–1614.
Monia, B.P., Haskell, K.M., Ecker, J.R., Ecker, D.J. and Crooke, S.T. 1989. Chromosomal mapping of the ubiquitin gene family in Saccharomyces cerevisiae by pulsed field gel electrophoresis. Nucleic Acids Res. 17: 3611.
Monia, B.P., Koser, P.L., Ecker, D.J. and Crooke, S.T. 1989. Studies on the expression of ubiquitin genes in yeast and mammalian cells. Submitted.
Muller-Taubenberger, A., Hagmann, J., Noegel, A. and Gerisch, G. 1988. Ubiquitin gene expression in Dictyostelium is induced by heat and cold shock, cadmium, and inhibitors of protein synthesis. J. Cell Sci. 90: 51–58.
Finley, D., Ozkaynak, E. and Varshavsky, A. 1987. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation and other tresses. Cell 48: 1035–1046.
Monia, B.P., Ecker, D.J., Jonnalagadda, S., Marsh, J., Gotlib, L., Butt, T.R. and Crooke, S.T. 1989. Gene synthesis, expression and processing of human ubiquitin carboxyl extension proteins. J. Biol. Chem. 264: 4093–4103.
Mayer, A.N. and Wilkinson, K.D., 1989. Detection, resolution and nomenclature of multiple ubiquitin carboxyl-terminal esterases from bovine calf thymus. Biochemistry 28: 166–172.
Jonnalagadda, S., Butt, T.R., Monia, B.P., Mirabelli, C.K., Gotlib, L., Ecker, D.J. and Crooke, S.T. 1989. Multiple (αNH-Ubiquitin) protein endoproteases in cells. J. Biol. Chem. 264: 10637–10642.
Redman, K.L. and Rechsteiner, M. 1988. Extended reading frame of a ubiquitin gene encodes a stable, conserved, basic protein. J. Biol. Chem. 263: 4926–4931.
Monia, B.P., Ecker, D.J. and Crooke, S.T. 1989. Identification of yeast CEP52 as a novel ribosomal protein of the large subunit. Submitted.
Jonnalagadda, S., Butt, T.R., Marsh, J., Sternberg, E.J., Mirabelli, C.K., Ecker, D.J. and Crooke, S.T. 1987. Expression and accurate processing of yeast pentaubiquitin in E. coli. J. Biol. Chem. 262: 17750–17756.
Lbpez-Otin, C., Simon-Mateo, C., Martinez, L. and Vinuela, E., 1989. Gly-Gly-X, a novel consensus sequence for the proteolytic processing of viral and cellular proteins. J. Biol. Chem. 264: 9107–9110.
Miller, H.I., Henzel, W.J., Ridgway, J.B., Kuang, W.J., Chisolm, V. and Liu, C.C. 1989. Cloning and expression of a yeast ubiquitin-protein cleaving activity in Escherichia coli. Bio/Technology 7: 698–704.
Vijay-Kumar, S., Bugg, C.E. and Cook, W.J. 1987. Structure of ubiquitin refined at 1.8 Å resolution. J. Mol. Biol. 194: 531–544.
Weber, P., Brown, S. and Mueller, L. 1987. 1H-NMR resonance assignments and secondary structure identification of human ubiquitin. Biochemistry 26: 7282–7290.
Finley, D., Ciechanover, A. and Varshavsky, A. 1984. Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85. Cell 37: 434–55.
Bachmair, A., Finley, D. and Varshavsky, A. 1986. In vivo half life of a protein is a function of its amino-terminal residue. Science 234: 179–186.
Hershko, A., Heller, H., Eytan, E., Kaklij, G. and Rose, I.A. 1984. Role of the α-amino group of protein in ubiquitin-mediated protein breakdown. Proc. Natl. Acad. Sci. USA 81: 70212–7025.
Ferber, S. and Ciechanover, A. 1986. 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.
Ferber, S. and Ciechanover, A. 1987. Role of arginine-tRNA in protein degradation by the ubiquitin pathway. Nature 326: 808–811.
Mayer, A., Siegel, N.R., Schwartz, A.L., Ciechanover, A. 1989. Degradation of proteins with acetylated amino termini by the ubiquitin system. Science 244: 1480–1483.
Hershko, A., Heller, H., Eytan, E. and Reiss, Y. 1986. The protein substrate binding site of the ubiquitin-proteins ligase system. J. Biol. Chem. 261: 11992–11999.
Varshavsky, A., Bachmair, A., Finley, D., Gonda, D. and Wunning, I. 1988. Ubiquitin. Rechstiner, M. (Ed.). Plenum Publishing Corp., New York.
Ecker, D.J., Butt, T.R., Marsh, J., Sternberg, E.J., Margolis, N., Monia, B.P., Jonnalagadda, S., Khan, M.I., Weber, D.L., Mueller, L. and Crooke, S.T. 1987. Gene synthesis, expression, structures and functional activities of site-specific mutants of ubiquitin. J. Biol. Chem. 262: 14213–14221.
Haas, A.L. and Bright, P.M. 1985. The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates. J. Biol. Chem. 260: 12464–12473.
Wilkinson, K.D. and Mayer, A.N. 1986. Alcohol-induced conformational changes of ubiquitin. Arch. Biochem. Biophys. 250: 390–399.
Ecker, D.J., Butt, T.R., Marsh, J., Sternberg, E.J., Shatzman, A., Dixon, J.S. and Crooke, S.T. 1989. Ubiquitin function studied by disulfide engineering. J. Biol. Chem. 264: 1887–1893.
Hershko, A. and Heller, H. 1985. Occurence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Commun. 128: 1079–1086.
Chau, V., Tobias, J.W., Bachmair, A., Marriott, D., Ecker, D.J., Conda, D.K. and Varshavsky, A. 1989. A multiubiquitin chain is confined to a specific lysine in a targeted short-lived protein. Science 243: 1576–1583.
Goldknopf, I.L. and Busch, H. 1977. Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proc. Natl. Acad. Sci. USA 74: 864–868.
Mueller, R.D., Yasuda, H., Hatch, C.L., Bonner, W.M., Bradbury, E.M. 1985. Identification of ubiquitinated histones 2A and 2B in Physarum polycephalum: Disappearance of these proteins at metaphare and reappearance at anaphase. J. Biol. Chem. 260: 5147–5153.
Levinger, L. and Varshavsky, A. 1982. Selective arrangement of ubiquitinated and D1 protein-containing nucleosomes within the Diosophila genome. Cell 28: 375–385.
Nickel, B.E., Allis, C.D. and Davie, J.R. 1989. Ubiquitinated histone H2B is preferentially located in transcriptionally active chromatin. Biochemistry 28: 958–963.
Nickel, B.E. and Davie, J.R. 1989. Structure of polyubiquitinated histone H2A. Biochemistry 28: 964–968.
Redman, K.L. and Rechsteiner, M. 1989. Identification of the long ubiquitin extension as ribosomal protein S27a. Nature 338: 438–440.
Monia, B.P., Ecker, D.J., Finley, D. and Crooke, S.T. 1989. Complementation of a yeast ubiquitin carboxyl extension mutant by its human homolog. Submitted.
Finley, D., Barte, B. and Varshavsky, A. 1989. The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature 338: 394–401.
Butt, T.R., Jonnalagadda, S., Monia, B.P., Sternberg, E.J., Marsh, J., Stadel, J.M., Ecker, D.J. and Crooke, S.T. 1989. Ubiquitin fusion augments the yield of cloned gene products in Escherichia coli. Proc. Natl. Acad. Sci. USA 86: 2540–2544.
Ecker, D.J., Stadel, J.M., Butt, T.R., Marsh, J.A., Monia, B.P., Powers, D.A., Gorman, J.A., Clark, P.E., Warren, F., Shatzman, A. and Crooke, S.T. 1989. Increasing gene expression in yeast by fusion to ubiquitin. J. Biol. Chem. 264: 7715–7719.
Sabin, E.A., Lee-Ng, C.T., Shuster, J.R. and Barr, P.J. 1989. High-level expression and in vivo processing of chimeric ubiquitin fusion proteins in Saccharomyces cerevisiae. Bio Technology 7: 705–709.
Warner, J.R. 1982. The Molecular Biology of the Yeast Saccharomyces. Strathern, J. N., Jones, E. W., Broach, J. R. (Eds.). Cold Spring Harbor Laboratory, New York.
Siegelman, M., Bond, M.W., Gallatin, W.M., St. John, T., Smith, H.T., Fried, V.A. and Weissman, I.L. 1986. Cell surface molecule associated with lymphocyte homing is a ubiquitinated branched-chain glycoprotein. Science 231: 823–829.
Yardin, Y., Escobedo, J.A., Kuang, W.-J., Yang-Ferng, T.L., Daniel, T.O., Tremble, P.M., Cheng, E.Y., Ando, M.E., Harkins, R.N., Francke, U., Fried, V.A., Ullrich, A. and Williams, L.T. 1986. Structure of the receptor for platelet derived growth factor helps define a family of closely related growth factor receptors. Nature 323: 226–232.
Leung, D.W., Spencer, S.A., Cachianes, G., Hammonds, R.G., Collings, C., Henzel, W.J., Barnard, R., Waters, M.J. and Wood, W.I. 1987. Growth hormone receptor and serum binding protein: Purification, cloning and expression. Nature 330: 537–543.
Gorin, E. and Goodman, H.M. 1985. Turnover of growth hormone receptors in rat adipocytes. Endocrinology 116: 1796–1805.
Huang, S.Y., Barnard, M.B., Xu, M., Matsui, S.I., Rose, S.M. and Garrard, W.T. 1986. The active immunoglobulin kappa chain gene is packaged by non-ubiquitin-conjugated nucleosomes. Proc. Natl. Acad. Sci. USA 83: 3738–3742.
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Monia, B., Ecker, D. & Crooke, S. New Perspectives on the Structure and Function of Ubiquitin. Nat Biotechnol 8, 209–215 (1990). https://doi.org/10.1038/nbt0390-209
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DOI: https://doi.org/10.1038/nbt0390-209
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