Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19096, USA.
Oncogene. 2011 Mar 3;30(9):1108-16. doi: 10.1038/onc.2010.462. Epub 2010 Oct 25.
SUMOylation governs numerous cellular processes and is essential to most eukaryotic life. Despite increasing recognition of the importance of this process, an extremely limited number of small ubiquitin-like modifier (SUMO) protein ligases (E3s) have been identified. Here we show that at least some members of the functionally diverse tripartite motif (TRIM) superfamily are SUMO E3s. These TRIM proteins bind both the SUMO-conjugating enzyme Ubc9 and substrates and strongly enhance transfer of SUMOs from Ubc9 to these substrates. Among the substrates of TRIM SUMO E3s are the tumor suppressor p53 and its principal antagonist Mdm2. The E3 activity depends on the TRIM motif, suggesting it to be the first widespread SUMO E3 motif. Given the large number of TRIM proteins, our results may greatly expand the identified SUMO E3s. Furthermore, TRIM E3 activity may be an important contributor to SUMOylation specificity and the versatile functions of TRIM proteins.
SUMOylation 调控着众多细胞过程,对大多数真核生物的生命都是必不可少的。尽管人们越来越认识到这一过程的重要性,但已鉴定出的小泛素样修饰物(SUMO)蛋白连接酶(E3s)数量极其有限。在这里,我们表明,功能多样的三联基序(TRIM)超家族的至少一些成员是 SUMO E3。这些 TRIM 蛋白既结合 SUMO 连接酶 Ubc9,又结合底物,并大大增强了 SUMO 从 Ubc9 向这些底物的转移。TRIM SUMO E3 的底物包括肿瘤抑制因子 p53 及其主要拮抗剂 Mdm2。E3 活性依赖于 TRIM 基序,这表明它是第一个广泛存在的 SUMO E3 基序。鉴于 TRIM 蛋白数量众多,我们的结果可能会大大扩展已鉴定的 SUMO E3。此外,TRIM E3 活性可能是 SUMOylation 特异性和 TRIM 蛋白多功能性的重要贡献者。