Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Sci Adv. 2023 Jan 27;9(4):eadd4969. doi: 10.1126/sciadv.add4969.
Transcription factor CP2c (also known as TFCP2, α-CP2, LSF, and LBP-1c) is involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies such as cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover an unprecedented mechanism of CP2c degradation via a previously unidentified SUMO1/PSME3/20 proteasome pathway and its biological meaning. CP2c is SUMOylated in a SUMO1-dependent way, and SUMOylated CP2c is degraded through the ubiquitin-independent PSME3 (also known as REGγ or PA28)/20 proteasome system. SUMOylated PSME3 could also interact with CP2c to degrade CP2c via the 20 proteasomal pathway. Moreover, precisely timed degradation of CP2c via the SUMO1/PSME3/20 proteasome axis is required for accurate progression of the cell cycle. Therefore, we reveal a unique SUMO1-mediated uncanonical 20 proteasome degradation mechanism via the SUMO1/PSME3 axis involving mutual SUMO-SIM interaction of CP2c and PSME3, providing previously unidentified mechanistic insights into the roles of dynamic degradation of CP2c in cell cycle progression.
转录因子 CP2c（也称为 TFCP2、α-CP2、LSF 和 LBP-1c）参与多种普遍存在的组织/阶段特异性细胞过程以及人类恶性肿瘤，如癌症。尽管它很重要，但 CP2c 的许多基本调控机制仍不清楚。在这里，我们通过以前未识别的 SUMO1/PSME3/20 蛋白酶体途径及其生物学意义揭示了 CP2c 降解的一种前所未有的机制。CP2c 以 SUMO1 依赖的方式被 SUMO 化，SUMO 化的 CP2c 通过非泛素依赖的 PSME3（也称为 REGγ 或 PA28）/20 蛋白酶体系统降解。SUMO 化的 PSME3 还可以与 CP2c 相互作用，通过 20 蛋白酶体途径降解 CP2c。此外，通过 SUMO1/PSME3/20 蛋白酶体轴对 CP2c 进行精确的时空调控降解是细胞周期精确进展所必需的。因此，我们揭示了一种独特的 SUMO1 介导的非典型 20 蛋白酶体降解机制，通过 SUMO1/PSME3 轴涉及 CP2c 和 PSME3 的 SUMO-SIM 相互作用，为 CP2c 在细胞周期进展中的动态降解作用提供了以前未知的机制见解。
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