| Literature DB >> 30008322 |
Lan Fang1, Hongqi Teng1, Yilin Wang2, Guanghong Liao3, Linjun Weng1, Yaxu Li1, Xinbo Wang1, Jiali Jin1, Chenchen Jiao1, Lei Chen1, Xiaoping Peng1, Jiayu Chen4, Yongzhi Yang1, Houqin Fang3, Dongyan Han1, Cheng Li1, Xueling Jin5, Shihao Zhang6, Zhongchen Liu1, Min Liu7, Qing Wei1, Lujian Liao3, Xin Ge1, Bin Zhao8, Dawang Zhou6, Huan-Long Qin1, Jun Zhou7, Ping Wang9.
Abstract
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.Entities:
Keywords: SET1A; YAP methylation; nuclear export; tumorigenesis
Mesh：
Substances：
Year: 2018 PMID： 30008322 DOI： 10.1016/j.ccell.2018.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743