SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway
SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway
复制标题
MCL1 蛋白的 SUMO 化通过调节泛素-蛋白酶体途径增强其稳定性
DOI：
10.1016/j.cellsig.2020.109686
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发表时间：
2020-09-01
影响因子：
4.8
通讯作者：
Wu, Huijian
中科院分区：
文献类型：
--
作者：
Li, Shujing;Wang, Jin;Wu, Huijian
在癌症中，通过促细胞凋亡和抗细胞凋亡细胞内信号的失调而引起的细胞凋亡逃避是反复发生的事件。因此，特异性蛋白质的选择性抑制代表了令人兴奋的治疗机会。髓样细胞白血病1（MCL 1）是BCL-2家族的抗凋亡蛋白，其在许多癌症中过表达。在这里，我们证明了MCL 1可以被K234和K238位点的小泛素样修饰物（SUMO）修饰。MCL 1的SUMO化可以通过抑制由包含三分基序的11（TRIM 11，我们在本研究中鉴定的一种新的MCL 1泛素E3连接酶）介导的MCL 1泛素-蛋白酶体途径来提高其稳定性。此外，MCL 1的SUMO化通过抑制细胞凋亡来增加癌细胞的增殖。这些结果表明，MCL 1的SUMO化可能在其功能的调节中发挥重要作用。
In cancers, apoptosis evasion through dysregulation of pro-apoptotic and anti-apoptotic intracellular signals is a recurring event. Accordingly, selective inhibition of specific proteins represents an exciting therapeutic opportunity. Myeloid cell leukemia 1 (MCL1) is an anti-apoptotic protein of the BCL-2 family, which is overexpressed in many cancers. Here, we demonstrate that MCL1 can be modified by the small ubiquitin-like modifier (SUMO) at K234 and K238 sites. The SUMOylation of MCL1 can improve its stability by inhibiting the MCL1 ubiquitin-proteasome pathway mediated by the Tripartite motif-containing 11 (TRIM11, a novel MCL1 ubiquitin E3 ligase that we identify in this study). Moreover, SUMOylation of MCL1 increases the proliferation of cancer cells by inhibiting apoptosis. These results suggest that the SUMOylation of MCL1 may play a significant role in the regulation of its function.