SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway

• Published in: Cellular signalling 2020-09, Vol.73, p.109686-109686, Article 109686
• Main Authors: Li, Shujing, Wang, Jin, Hu, Gaolei, Aman, Sattout, Li, Bowen, Li, Yanan, Xia, Kangkai, Yang, Yuxi, Ahmad, Bashir, Wang, Miao, Wu, Huijian
• Format: Article
• Language: English
• Subjects: Apoptosis; MCL1; Proliferation; SUMOylation; Ubiquitination
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2020.109686

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. •MCL1 can be modified by SUMOs•MCL1 SUMOylation upregulatesits stability•TRIM11 is a novelubiquitin E3 ligase of MCL1•SUMOylation of MCL1 inhibits TRIM11-mediated MCL1 ubiquitination•SUMOylation of MCL1 promotes theproliferation ofcancer cells