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PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose induction in hepatocellular carcinoma.


ABSTRACT: Although cancer cells are known to be "addicted" to glucose, the effect of glucose in proliferation of these cells remains elusive. Here, we report that upon glucose induction, protein arginine methyltransferase 5 (PRMT5) exerts a profound effect on the G1-S cell cycle progression via directly interacting with cyclin dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC). Upregulation of both PRMT5 and CDK4 predicts more malignant characteristics in human HCC tissues. Mechanistically, glucose promotes the interaction between PRMT5 and CDK4, which leads to activation of CDK4-RB-E2F-mediated transcription via releasing CDKN2A from CDK4. Moreover, the PRMT5 competitive inhibition of the interaction between CDK4 and CDKN2A is important for glucose-induced growth of HCC cells. Furthermore, the CDK4 mutant R24A weakly binds to PRMT5, inhibiting HCC cell cycle progression and tumor growth. Thus, our findings uncover a critical function for PRMT5 and CDK4 and provide an improved therapeutic strategy against HCC.

SUBMITTER: Yang H 

PROVIDER: S-EPMC5342150 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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PRMT5 competitively binds to CDK4 to promote G1-S transition upon glucose induction in hepatocellular carcinoma.

Yang Hao H   Zhao Xiaoping X   Zhao Li L   Liu Liu L   Li Jiajin J   Jia Wenzhi W   Liu Jianjun J   Huang Gang G  

Oncotarget 20161101 44


Although cancer cells are known to be "addicted" to glucose, the effect of glucose in proliferation of these cells remains elusive. Here, we report that upon glucose induction, protein arginine methyltransferase 5 (PRMT5) exerts a profound effect on the G1-S cell cycle progression via directly interacting with cyclin dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC). Upregulation of both PRMT5 and CDK4 predicts more malignant characteristics in human HCC tissues. Mechanistically, gluco  ...[more]

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