The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer | |
Chen, Min1; Zhang, Hui1; Shi, Zhubing1; Li, Yehua1; Zhang, Xiaoman1; Gao, Ziyang1; Ma, Jian1; Xu, Qi1; Guan, Jingmin1; Jiao, Shi1 | |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY |
2018 | |
卷号 | 293期号:37页码:14455-14469 |
关键词 | Organ Size Control Cell-proliferation Kinase Mst4 Promotes Apoptosis Stripak Complexes Dendritic Spines Human Mob1 Protein Phosphorylation Activation |
ISSN号 | 0021-9258 |
DOI | 10.1074/jbc.RA118.003279 |
文献子类 | Article |
英文摘要 | The mammalian STE20-like protein kinase 1 (MST1)-MOB kinase activator 1 (MOB1) complex has been shown to suppress the oncogenic activity of Yes-associated protein (YAP) in the mammalian Hippo pathway, which is involved in the development of multiple tumors, including pancreatic cancer (PC). However, it remains unclear whether other MST-MOB complexes are also involved in regulating Hippo-YAP signaling and have potential roles in PC. Here, we report that mammalian STE20-like kinase 4 (MST4), a distantly related ortholog of the MST1 kinase, forms a complex with MOB4 in a phosphorylation-dependent manner. We found that the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex, even though the two complexes exhibited opposite biological functions in PC. In contrast to the tumor-suppressor effect of the MST1-MOB1 complex, the MST4-MOB4 complex promoted growth and migration of PANC-1 cells. Moreover, expression levels of MST4 and MOB4 were elevated in PC and were positively correlated with each other, whereas MST1 expression was down-regulated. Because of divergent evolution of key interface residues, MST4 and MOB4 could disrupt assembly of the MST1-MOB1 complex through alternative pairing and thereby increased YAP activity. Collectively, these findings identify the MST4-MOB4 complex as a noncanonical regulator of the Hippo-YAP pathway with an oncogenic role in PC. Our findings highlight that although MST-MOB complexes display some structural conservation, they functionally diverged during their evolution. |
电子版国际标准刊号 | 1083-351X |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000444671500024 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3498] |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Zhou, Zhaocai |
作者单位 | 1.Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci,State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 3.Fudan Univ, Zhongshan Hosp, Dept Hematol, Shanghai 200032, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Inst Clin Sci, Shanghai 200032, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Min,Zhang, Hui,Shi, Zhubing,et al. The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(37):14455-14469. |
APA | Chen, Min.,Zhang, Hui.,Shi, Zhubing.,Li, Yehua.,Zhang, Xiaoman.,...&Cheng, Yunfeng.(2018).The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.JOURNAL OF BIOLOGICAL CHEMISTRY,293(37),14455-14469. |
MLA | Chen, Min,et al."The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer".JOURNAL OF BIOLOGICAL CHEMISTRY 293.37(2018):14455-14469. |
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