硫氧化物9
转录因子
染色体易位
细胞生物学
调节器
核出口信号
核运输
癌症研究
生物
化学
细胞核
细胞质
遗传学
基因
作者
Wenrong Xu,Chen‐Hong Ding,Fang Liu,Shijie Chen,Chia-Chi Flora Huang,Meng‐Chao Xiao,Xialu Hong,Mingchen Wang,Fang‐Zhi Yan,Kai Ding,Yalu Cui,Bai-Nan Zheng,Jingzhong Ding,Cheng Luo,Xin Zhang,Wei‐Fen Xie
标识
DOI:10.1038/s41392-024-01805-4
摘要
Abstract The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.
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