期刊
BIOCHEMICAL JOURNAL
卷 453, 期 -, 页码 137-145出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130244
关键词
E2 ubiquitin-conjugating enzyme; N-terminal modification; RNF4 (RING finger protein 4); SUMO (small ubiquitin-related modifier); ubiquitin; ubiquitin-conjugating enzyme E2W (Ube2W)
资金
- Cancer Research UK [C434/A13067]
- Wellcome Trust [098391/Z/12/Z]
- Cancer Research UK [13067] Funding Source: researchfish
- Wellcome Trust [098391/Z/12/Z] Funding Source: researchfish
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.
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