Characterization of the ubiquitin-specific protease activity of the mouse/human Unp/Unph oncoprotein

Catherine A. Gilchrist, Rohan T. Baker

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    22 Citations (Scopus)

    Abstract

    The ubiquitin-specific proteases (Ubps) are a family of largely dissimilar enzymes with two major conserved sequence regions, containing either a conserved cysteine residue or two conserved histidine residues, respectively. The murine Unp oncoprotein and its human homologue, Unph, both contain regions similar to the conserved Cys and His boxes common to all the Ubps. In this study we show that Unp and Unph are active deubiquitinating enzymes, being able to cleave ubiquitin from both natural and engineered linear ubiquitin-protein fusions, including the polyubiquitin precursor. Mutation of the conserved Unp Cys and His residues abolishes this activity, and identifies the likely His residue in the catalytic triad. Unp is tumorigenic when overexpressed in mice, leading to the suggestion that Unp may play a role in the regulation of ubiquitin-dependent protein degradation. We have demonstrated here that the high-level expression of Unp in yeast does not disrupt the degradation of the N-end rule substrate Tyr-β-galactosidase (βgal), the non-N-end rule substrate ubiquitin-Pro-βgal, or the degradation of abnormal, canavanine-containing proteins. These data suggest that Unp is not a general modulator of ubiquitin-dependent proteolysis. However, Unp may have a role in the regulation of the degradation of a specific, as yet undescribed, substrate(s). (C) 2000 Elsevier Science B.V.

    Original languageEnglish
    Pages (from-to)297-309
    Number of pages13
    JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
    Volume1481
    Issue number2
    DOIs
    Publication statusPublished - 29 Sept 2000

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