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Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.

ABSTRACT: Many mutant p53 proteins (mutp53s) exert oncogenic gain-of-function (GOF) properties, but the mechanisms mediating these functions remain poorly defined. We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells. Conversely, downregulation of GOF mutp53s enhances AMPK activation under energy stress, decreasing the activity of the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 and inhibiting aerobic glycolytic potential and invasive cell growth. Under conditions of energy stress, GOF mutp53s, but not wild-type p53, preferentially bind to the AMPK? subunit and inhibit AMPK activation. Given the importance of AMPK as an energy sensor and tumor suppressor that inhibits anabolic metabolism, our findings reveal that direct inhibition of AMPK activation is an important mechanism through which mutp53s can gain oncogenic function.

SUBMITTER: Zhou G

PROVIDER: S-EPMC4067806 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.

Zhou Ge G Wang Jiping J Zhao Mei M Xie Tong-Xin TX Tanaka Noriaki N Sano Daisuke D Patel Ameeta A AA Ward Alexandra M AM Sandulache Vlad C VC Jasser Samar A SA Skinner Heath D HD Fitzgerald Alison Lea AL Osman Abdullah A AA Wei Yongkun Y Xia Xuefeng X Songyang Zhou Z Mills Gordon B GB Hung Mien-Chie MC Caulin Carlos C Liang Jiyong J Myers Jeffrey N JN

Molecular cell 20140522 6

Many mutant p53 proteins (mutp53s) exert oncogenic gain-of-function (GOF) properties, but the mechanisms mediating these functions remain poorly defined. We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells. Conversely, downregulation of GOF mutp53s enhances AMPK activation under energy stress, decreasing the activity of the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 and inhibiting aerobic glycolytic potential and ...[more]

PMID: 24857548

Dataset Information

Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.

Publications

Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.

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