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.

在癌症中，通过促凋亡和抗凋亡细胞内信号的失调来逃避凋亡是一个反复发生的事件。因此，特定蛋白质的选择性抑制代表了令人兴奋的治疗机会。髓细胞白血病 1 (MCL1) 是 BCL-2 家族的一种抗凋亡蛋白，在许多癌症中过度表达。在这里，我们证明 MCL1 可以通过 K234 和 K238 位点的小泛素样修饰符 (SUMO) 进行修饰。MCL1 的 SUMOylation 可以通过抑制由包含三方基序的 11（TRIM11，我们在本研究中鉴定的新型 MCL1 泛素 E3 连接酶）介导的 MCL1 泛素-蛋白酶体途径来提高其稳定性。此外，MCL1 的 SUMOylation 通过抑制细胞凋亡来增加癌细胞的增殖。