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. Author manuscript; available in PMC: 2005 Nov 1.
Published in final edited form as: Nat Cell Biol. 2005 Aug;7(8):750–757. doi: 10.1038/ncb0805-750

Figure 1.

Figure 1

Mechanisms of protein modification by ubiquitin (a) and Ubl proteins (b). (a) Protein substrates are modified by ubiquitin and Ubl-proteins at a lysine (K) residue(s). (1) Ubiquitin attachment to a substrate is catalyzed by the coordinated actions of an E1[dk29] activating enzyme, E2 conjugating enzyme, and E3 ligase (2) Poly- ubiquitin chains can be formed through any of 7 lysine residues within ubiquitin. Deubiquitinating enzymes (DUBs) reverse ubiquitination and shorten poly-ubiquitin chains. (3) A subset of factors, termed E4 enzymes, can further lengthen poly- ubiquitin chains. (4, 5) Degradation of ubiquitinated proteins occurs through a mechanism largely dependent on ubiquitin-ubiquitin linkages formed through K48 of ubiquitin. Poly- ubiquitin chain binding proteins such as Rad23/Hhr23 and Dsk2/Ubiquilin[dk30] facilitate recognition and degradation of ubiquitinated substrates by the 26S proteasome. Substrate modifications by mono-ubiquitin, K63-linked chains, or by Ubl-proteins (b) regulate a series of proteasome independent cellular processes. Biological significance of other ubiquitin linkages and many Ubl proteins remain poorly characterized. (b) [dk31](1) Ubl attachment occurs through a mechanism analogous to ubiquitination, involving E1, E2, and E3 enzymes. Ubl deconjugating enzymes remove Ubl modifications from substrates. (2) Poly-Ubl chains can be formed for SUMO. Poly-chain formation for other Ubls is currently under investigation. Modification by Ubl proteins can block ubiquitination sites, activate enzymes (including Ub E3 ligases), and affect protein localization.