Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200025, China,
Mol Cell Biochem. 2014 Jan;385(1-2):69-77. doi: 10.1007/s11010-013-1815-3. Epub 2013 Oct 6.
SUMOylation has been considered as an important mechanism to regulate multiple cellular processes, including inflammation. TAB2 (TAK1-binding protein 2) is an upstream adaptor protein in the IL-1 signaling pathway. Covalent modifications of TAB2 have not been well studied. In this study, we demonstrated that TAB2 could be modified by SUMO. Using Ubc9 (SUMO-conjugating enzyme) fusion and mutation analysis, we identified evolutionarily conserved lysine 329 as the major SUMOylation site of TAB2. PIAS3, a SUMO E3 ligase, preferentially interacted with and promoted its SUMOylation. Interestingly, block of SUMOylation by mutation of lysine 329 enhanced the activity of TAB2, as reflected by AP-1 luciferase reporter assays. Taken together, these results suggest that SUMOylation may serve as a novel mechanism for the regulation of TAB2.
SUMOylation 被认为是调节多种细胞过程的重要机制，包括炎症。TAB2（TAK1 结合蛋白 2）是 IL-1 信号通路中的上游衔接蛋白。TAB2 的共价修饰尚未得到很好的研究。在这项研究中，我们证明 TAB2 可以被 SUMO 修饰。通过 Ubc9（SUMO 连接酶）融合和突变分析，我们确定了进化上保守的赖氨酸 329 是 TAB2 的主要 SUMOylation 位点。PIAS3，一种 SUMO E3 连接酶，优先与 TAB2 相互作用并促进其 SUMOylation。有趣的是，通过突变赖氨酸 329 阻断 SUMOylation增强了 TAB2 的活性，如 AP-1 荧光素酶报告基因分析所反映的那样。总之，这些结果表明 SUMOylation 可能是 TAB2 调节的一种新机制。
