CREPT Accelerates Tumorigenesis by Regulating the Transcription of Cell-Cycle-Related Genes

被引：129

作者：

Lu, Dongdong ^{[1
,2
]}

Wu, Yinyuan ^{[1
]}

Wang, Yinyin ^{[1
]}

Ren, Fangli ^{[1
]}

Wang, Dianjun ^{[3
,4
]}

Su, Fuqin ^{[1
]}

Zhang, Yanquan ^{[1
]}

Yang, Xi ^{[1
]}

Jin, Guihua ^{[1
]}

Hao, Xinbao ^{[1
]}

He, Dacheng ^{[5
]}

Zhai, Yonggong ^{[5
]}

Irwin, David M. ^{[6
]}

Hu, Jim ^{[7
]}

Sung, Joseph J. Y. ^{[8
,9
]}

Yu, Jun ^{[8
,9
]}

Jia, Baoqing ^{[3
,4
]}

Chang, Zhijie ^{[1
]}

机构：

[1] Tsinghua Univ, Sch Med, State Key Lab Biomembrane & Membrane Biotechnol, Natl Engn Lab Antitumor Therapeut, Beijing 100084, Peoples R China

[2] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China

[3] Chinese Peoples Liberat Army Gen Hosp, Dept Surg Oncol, Beijing 100853, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing 100853, Peoples R China

[5] Beijing Normal Univ, Sch Life Sci, Beijing 100874, Peoples R China

[6] Univ Toronto, Dept Lab Med & Pathobiol, Kings Coll Circle 1, Toronto, ON M5S 1A8, Canada

[7] Hosp Sick Children, Res Inst, Physiol & Expt Med Program, Toronto, ON M5G 1X8, Canada

[8] Chinese Univ Hong Kong, Inst Digest Dis, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China

[9] Chinese Univ Hong Kong, Dept Med & Therapeut, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China

来源：

CANCER CELL | 2012年 / 21卷 / 01期

关键词：

RNA-POLYMERASE-II; CANCER-THERAPY; DEPENDENT KINASES; MAMMALIAN-CELLS; CDK INHIBITORS; BREAST-CANCER; ONCOGENES; TARGETS; TUMOR; PART;

D O I：

10.1016/j.ccr.2011.12.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumorigenesis is caused by an uncontrolled cell cycle and the altered expression of many genes. Here, we report a gene CREPT that is preferentially expressed in diverse human tumors. Overexpression of CREPT accelerates tumor growth, whereas depletion of CREPT demonstrates a reversed effect. CREPT regulates cyclin D1 expression by binding to its promoter, enhancing its transcription both in vivo and in vitro, and interacting with RNA polymerase II (RNAPII). Interestingly, CREPT promotes the formation of a chromatin loop and prevents RNAPII from reading through the 3' end termination site of the gene. Our findings reveal a mechanism where CREPT increases cyclin D1 transcription during tumorigenesis, through enhancing the recruitment of RNAPII to the promoter region, possibly, as well as chromatin looping.

引用

页码：92 / 104

页数：13

共 40 条

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Going on a cancer gene hunt [J].