Ube2W conjugates ubiquitin to α-amino groups of protein N-termini

Michael H. Tatham, Anna Plechanovova, Ellis G. Jaffray, Helena Salmen, Ronald T. Hay

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    57 Citations (Scopus)

    Abstract

    The covalent attachment of the protein ubiquitin to intracellular proteins by a process known as ubiquitylation regulates almost all major cellular systems, predominantly by regulating protein turnover. Ubiquitylation requires the co-ordinated action of three enzymes termed E1, E2 and E3, and typically results in the formation of an isopeptide bond between the C-terminal carboxy group of ubiquitin and the epsilon-amino group of a target lysine residue. However, ubiquitin is also known to conjugate to the thiol of cysteine residue side chains and the alpha-amino group of protein N-termini, although the enzymes responsible for discrimination between different chemical groups have not been defined. In the present, study, we show that Ube2W (Ubc16) is an E2 ubiquitin-conjugating enzyme with specific protein N-terminal mono-ubiquitylation activity. Ube2W conjugates ubiquitin not only to its own N-terminus, but also to that of the small ubiquitin-like modifier SUMO (small ubiquitin-related modifier) in a manner dependent on the SUMO-targeted ubiquitin ligase RNF4 (RING finger protein 4). Furthermore, N-terminal mono-ubiquitylation of SUMO-2 primes it for poly-ubiquitylation by the Ubc13-UEV1 (ubiquitin-conjugating enzyme E2 variant 1) heterodimer, showing that N-terminal ubiquitylation regulates protein fate. The description in the present study is the first of an E2-conjugating enzyme with N-terminal ubiquitylation activity, and highlights the importance of E2 enzymes in the ultimate outcome of E3-mediated ubiquitylation.

    Original languageEnglish
    Pages (from-to)137-145
    Number of pages9
    JournalBiochemical Journal
    Volume453
    Issue number1
    DOIs
    Publication statusPublished - 2013

    Keywords

    • N-terminal modification
    • PML
    • ubiquitin-conjugating enzyme E2W (Ube2W)
    • E3 LIGASE
    • DNA-DAMAGE
    • ubiquitin
    • PATHWAY
    • SUMO (small ubiquitin-related modifier)
    • SITE
    • RESIDUE
    • RNF4
    • CHIP
    • DEGRADATION
    • RNF4 (RING finger protein 4)
    • E2 ubiquitin-conjugating enzyme

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