The Deubiquitinating Enzymes
As detailed elsewhere in this volume, modification of proteins by the 76-residue ubiquitin polypeptide is involved in many aspects of protein metabolism. Among the cellular processes affected by ubiquitin-dependent reactions are chromosome structure and segregation, cell-cycle progression, receptor-mediated signal transduction, gene expression, protein localization, organelle biogenesis, antigen presentation, viral pathogenesis, and the stress response (reviewed in Hochstrasser, 1995, 1996a; Rubin and Finley, 1995; Wilkinson, 1995; Ciechanover, 1994; Hershko and Ciechanover, 1992; Finley and Chau, 1991). One type of ubiquitination, attachment of a polyubiquitin chain(s) to a protein, targets the modified protein for proteolysis by the proteasome (see references above). The ubiquitin molecules in these polyubiquitin chains are most often linked to one another by isopeptide bonds between the C-terminus of one ubiquitin and the e-amino group of lysine 48 of the next ubiquitin (Chau et al., 1989; Gregori et al., 1990; Hochstrasser et al., 1991). There is also evidence that polyubiquitin chains can be formed with isopeptide linkages involving lysines 6, 11 (Baboshina and Haas, 1996), 29 (Arnason and Ellison, 1994), or 63 (Arnason and Ellison, 1994; Spence et al., 1995) of ubiquitin. In addition, a variety of ubiquitinlike proteins have been described (Toniolo et al., 1988; Banerji et al., 1990; Meyers et al., 1991; Kumar et al., 1993; Olvera and Wool, 1993; Linnen et al., 1993; Haas et al., 1996; Nakamura et al., 1996; Narasimhan et al., 1996; Biggins et al., 1996; Shen et al., 1996).
KeywordsHydrolysis Amide Glycine Cysteine Aldehyde
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