Sun Xiao-Xin, Li Yanping, Sears Rosalie C, Dai Mu-Shui
Department of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States.
Front Oncol. 2021 Jun 11;11:679445. doi: 10.3389/fonc.2021.679445. eCollection 2021.
Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.
MYC的异常过表达和激活促进肿瘤生长和进展。鉴于MYC蛋白半衰期短且性质不稳定,这种癌蛋白受到多种翻译后机制的高度调控也就不足为奇了。其中,泛素化在正常细胞生长和稳态过程中动态控制MYC的水平和活性,而泛素化/去泛素化平衡的紊乱会导致MYC不必要的稳定和激活。此外,MYC还受到SUMO化的调控,SUMO化与泛素化途径相互作用,控制MYC蛋白的稳定性和活性。在本综述中,我们将总结关于MYC泛素化的最新进展,并探讨这些MYC调节剂作为癌症潜在治疗靶点的前景。