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Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding 期刊论文

编号：

d3386eab-7b55-4862-a25a-6d179cd8d679
作者：

Liao, Peng^[1,2] Zeng, Shelya X.^[1,2] Zhou, Xiang^[1,2,7] Chen, Tianjian^[3] Zhou, Fen^[4] Cao, Bo^[1,2] Jung, Ji Hoon^[1,2] Del Sal, Giannino^[5,6] Luo, Shiwen^[4] Lu, Hua^[1,2]
语种：

English
期刊：

MOLECULAR CELL ISSN：1097-2765 2017 年 68 卷 6 期 (1134 - +) ; DEC 21
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摘要：

TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma(HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with mutations of four serines/threonines previously shown to be crucial for PIN1 binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1-p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC.
推荐引用方式
GB/T 7714：

Liao Peng,Zeng Shelya X.,Zhou Xiang, et al. Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding [J].MOLECULAR CELL,2017,68(6):1134-+.
APA：

Liao Peng,Zeng Shelya X.,Zhou Xiang,Chen Tianjian,&Lu Hua.(2017).Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding .MOLECULAR CELL,68(6):1134-+.
MLA：

Liao Peng, et al. "Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding" .MOLECULAR CELL 68,6(2017):1134-+.

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