SUMOylation-mediated PSME3-20 Proteasomal Degradation of Transcription Factor CP2c is Crucial for Cell Cycle Progression

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Jan 27

PMID 36706181

Authors

Seung Han Son

Min Young Kim

Young Su Lim

Hyeon Cheol Jin

June Ho Shin

Jae Kyu Yi

Sungwoo Choi

Mi Ae Park

Ji Hyung Chae

Ho Chul Kang

Young Jin Lee

Vladimir N Uversky

Chul Geun Kim

Affiliations

Soon will be listed here.

Abstract

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.

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