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

• Published in: Biochemical journal Vol. 453; no. 1; p. 137
• Main Authors: Tatham, Michael H, Plechanovová, Anna, Jaffray, Ellis G, Salmen, Helena, Hay, Ronald T
• Format: Journal Article
• Language: English
• Published: England 01.07.2013
• Subjects: Nuclear Proteins - metabolism; Small Ubiquitin-Related Modifier Proteins - metabolism; Transcription Factors - metabolism; Ubiquitin - metabolism; Ubiquitin-Conjugating Enzymes - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• DOI: 10.1042/BJ20130244

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 ϵ-amino group of a target lysine residue. However, ubiquitin is also known to conjugate to the thiol of cysteine residue side chains and the α-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.