SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis.

Cancer cell 2018 Jul 09

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YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Citation

Lan Fang, Hongqi Teng, Yilin Wang, Guanghong Liao, Linjun Weng, Yaxu Li, Xinbo Wang, Jiali Jin, Chenchen Jiao, Lei Chen, Xiaoping Peng, Jiayu Chen, Yongzhi Yang, Houqin Fang, Dongyan Han, Cheng Li, Xueling Jin, Shihao Zhang, Zhongchen Liu, Min Liu, Qing Wei, Lujian Liao, Xin Ge, Bin Zhao, Dawang Zhou, Huan-Long Qin, Jun Zhou, Ping Wang. SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis. Cancer cell. 2018 Jul 09;34(1):103-118.e9