CREPT/RPRD1B associates with Aurora B to regulate Cyclin B1 expression for accelerating the G2/M transition in gastric cancer

被引:53
作者
Ding, Lidan [1 ]
Yang, Liu [1 ]
He, Yuqi [2 ]
Zhu, Bingtao [1 ]
Ren, Fangli [1 ]
Fan, Xuanzi [1 ]
Wang, Yinyin [1 ]
Li, Mengdi [1 ]
Li, Jun [3 ]
Kuang, Yanshen [4 ]
Liu, Sihan [1 ]
Zhai, Wanli [1 ]
Ma, Danhui [1 ]
Ju, Yanfang [4 ]
Liu, Quentin [5 ]
Jia, Baoqing [4 ]
Sheng, Jianqiu [2 ]
Chang, Zhijie [1 ]
机构
[1] Tsinghua Univ, Sch Med, State Key Lab Membrane Biol, Beijing 100084, Peoples R China
[2] PLA Army Gen Hosp, Dept Gastroenterol, Beijing 100700, Peoples R China
[3] Third Mil Med Univ, PLA, Inst Immunol, Chongqing 400038, Peoples R China
[4] Chinese Peoples Liberat Army Gen Hosp, Dept Gen Surg Pathol, Beijing 100853, Peoples R China
[5] Sun Yat Sen Univ, State Key Lab Canc South China, Canc Ctr, Guangzhou 510275, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
CELL-CYCLE; CDK INHIBITORS; PROLIFERATION; GROWTH; TRANSCRIPTION; INCREASES; KINASES; P53;
D O I
10.1038/s41419-018-1211-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gastric cancer, like most of other cancers, has an uncontrolled cell cycle regulated by cyclins and cyclin-dependent kinases (CDKs). In this study, we reported that gastric cancer cells showed an accelerated G2/M transition promoted by CREPT/RPRD1B and Aurora kinase B (Aurora B). We found that CREPT/RPRD1B and Aurora B were coordinately expressed during the cell cycle in gastric cancer cells. Deletion of CREPT/RPRD1B disturbed the cell progression and extended the length of cell cycle, leading to a significant accumulation of mitotic cells. Mechanistically, we revealed that CREPT/RPRD1B interacted with Aurora B to regulate the expression of Cyclin B1 in gastric cancer cells. Interestingly, Aurora B phosphorylates S145 in a well-conserved motif of CREPT/RPRD1B. We proposed that phosphorylation of CREPT/RPRD1B by Aurora B is required for promoting the transcription of Cyclin B1, which is critical for the regulation of gastric tumorigenesis. Our study provides a mechanism by which gastric tumor cells maintain their high proliferation rate via coordination of Aurora B and CREPT/RPRD1B on the expression of Cyclin B1. Targeting the interaction of Aurora B and CREPT/RPRD1B might be a strategy for anti-gastric cancer therapy in the future.
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页数:15
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