Yinuo Wang, Aihua Mao, Jingwei Liu, Pengjie Li, Shaoqin Zheng, Tong Tong, Zexu Li, Haijiao Zhang, Lanjing Ma, Jiahui Lin, Zhongqiu Pang, Qing Han, Fukang Qi, Xinjun Zhang, Maorong Chen, Xi He, Xi Zhang, Teng Fei, Bi-Feng Liu, Daming Gao, Liu Cao, Qiang Wang, Yiwei Li, Ren Sheng
Wnt/β-catenin signaling is a conserved pathway crucially governing development, homeostasis, and oncogenesis. Discoveries of its regulators hold great values in both basic and translational research. Through screening, we identified a deubiquitinase, USP10, as a critical modulator of β-catenin. Mechanistically, USP10 binds to key scaffold Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination. Surprisingly, USP10 physically tethers Axin1 and β-catenin and promotes the phase separation for β-catenin suppression regardless of the enzymatic activity...
August 11, 2023: Cell Chemical Biology