Regulation of the Hippo-YAP Pathway by Glucose Sensor O-GlcNAcylation

被引：277

作者：

Peng, Changmin ^{[1
,2
]}

Zhu, Yue ^{[2
,3
,4
]}

Zhang, Wanjun ^{[2
]}

Liao, Qinchao ^{[1
]}

Chen, Yali ^{[2
]}

Zhao, Xinyuan ^{[2
]}

Guo, Qiang ^{[5
]}

Shen, Pan ^{[2
]}

Zhen, Bei ^{[2
]}

Qian, Xiaohong ^{[2
]}

Yang, Dong ^{[2
]}

Zhang, Jin-San ^{[5
]}

Xiao, Dongguang ^{[1
]}

Qin, Weijie ^{[2
]}

Pei, Huadong ^{[2
,6
]}

机构：

[1] Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin Ind Microbiol Key Lab, Key Lab Ind Fermentat Microbiol,Minist Educ, 29 13ST TEDA, Tianjin 300457, Peoples R China

[2] Beijing Inst Lifeom, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing 102206, Peoples R China

[3] Anhui Med Univ, Hefei 230032, Anhui, Peoples R China

[4] Beijing Inst Radiat Med, Beijing 102206, Peoples R China

[5] Wenzhou Med Univ, Sch Pharmaceut Sci, Cell Signaling & Epigenet Lab, Wenzhou 325035, Zhejiang, Peoples R China

[6] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, 2300 Eye St NW, Washington, DC 20037 USA

来源：

MOLECULAR CELL | 2017年 / 68卷 / 03期

基金：

中国国家自然科学基金;

关键词：

ORGAN SIZE CONTROL; AMPK-MEDIATED REGULATION; CELL CONTACT INHIBITION; GROWTH-CONTROL; TUMOR-SUPPRESSOR; CANCER; PROTEIN; PHOSPHORYLATION; GLYCOSYLATION; GLCNAC;

D O I：

10.1016/j.molcel.2017.10.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The Hippo pathway is crucial in organ size control and tissue homeostasis, with deregulation leading to cancer. An extracellular nutrition signal, such as glucose, regulates the Hippo pathway activation. However, the mechanisms are still not clear. Here, we found that the Hippo pathway is directly regulated by the hexosamine biosynthesis pathway (HBP) in response to metabolic nutrients. Mechanistically, the core component of Hippo pathway (YAP) is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 109. YAP O-GlcNAcylation disrupts its interaction with upstream kinase LATS1, prevents its phosphorylation, and activates its transcriptional activity. And this activation is not dependent on AMPK. We also identified OGT as a YAP-regulated gene that forms a feedback loop. Finally, we confirmed that glucose-induced YAP O-GlcNAcylation and activation promoted tumorigenesis. Together, our data establish a molecular mechanism and functional significance of the HBP in directly linking extracellular glucose signal to the Hippo-YAP pathway and tumorigenesis.

引用

页码：591 / +

页数：19

共 62 条

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