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

被引：147

作者：

Fang, Lan ^{[1
,2
]}

Teng, Hongqi ^{[1
,2
]}

Wang, Yilin ^{[3
,11
]}

Liao, Guanghong ^{[4
]}

Weng, Linjun ^{[1
,2
]}

Li, Yaxu ^{[1
,2
]}

Wang, Xinbo ^{[1
,2
]}

Jin, Jiali ^{[1
,2
]}

Jiao, Chenchen ^{[1
,2
]}

Chen, Lei ^{[1
,2
]}

Peng, Xiaoping ^{[1
,2
]}

Chen, Jiayu ^{[5
]}

Yang, Yongzhi ^{[1
,2
]}

Fang, Houqin ^{[4
]}

Han, Dongyan ^{[1
,2
]}

Li, Cheng ^{[1
,2
]}

Jin, Xueling ^{[6
]}

Zhang, Shihao ^{[7
]}

Liu, Zhongchen ^{[1
,2
]}

Liu, Min

Wei, Qing ^{[1
,2
]}

Liao, Lujian ^{[4
]}

Ge, Xin ^{[1
,2
]}

Zhao, Bin ^{[9
,10
]}

Zhou, Dawang ^{[7
]}

Qin, Huan-Long ^{[1
,2
]}

Zhou, Jun ^{[8
]}

Wang, Ping ^{[1
,2
]}

机构：

[1] Tongji Univ, Shanghai Peoples Hosp Tongji Univ 10, Sch Med, Shanghai 200072, Peoples R China

[2] Tongji Univ, Sch Life Sci & Technol, Shanghai 200072, Peoples R China

[3] Shanghai Canc Ctr, Dept Hepat Surg, Shanghai 200032, Peoples R China

[4] East China Normal Univ, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[5] Tongji Univ, Sch Life Sci & Technol, Shanghai 200072, Peoples R China

[6] Fudan Univ, Obstetr & Gynecol Hosp, Shanghai 200032, Peoples R China

[7] Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China

[8] Shandong Normal Univ, Coll Life Sci, Shandong Collaborat Innovat Ctr Cell Biol, Inst Biomed Sci,Shandong Prov Key Lab Anim Resist, Jinan 250014, Shandong, Peoples R China

[9] Zhejiang Univ, Life Sci Inst, Zhejiang 310058, Peoples R China

[10] Zhejiang Univ, Innovat Ctr Cell Signaling Network, Zhejiang 310058, Peoples R China

[11] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China

来源：

CANCER CELL | 2018年 / 34卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ORGAN SIZE CONTROL; CELL CONTACT INHIBITION; HIPPO PATHWAY; LYSINE METHYLATION; GROWTH-CONTROL; CANCER; PHOSPHORYLATION; METHYLTRANSFERASES; LOCALIZATION; STABILITY;

D O I：

10.1016/j.ccell.2018.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：103 / +

页数：25

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