Effect of Mutant p53 Proteins on Glycolysis and Mitochondrial Metabolism.

Autor:	Eriksson M; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Ambroise G; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Ouchida AT; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Lima Queiroz A; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Smith D; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Gimenez-Cassina A; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.; Departamento de Biología Molecular, Universidad Autónoma de Madrid, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Iwanicki MP; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA., Muller PA; MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom., Norberg E; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Erik.Norberg@ki.se Helin.norberg@ki.se., Vakifahmetoglu-Norberg H; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Erik.Norberg@ki.se Helin.norberg@ki.se.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2017 Nov 28; Vol. 37 (24). Date of Electronic Publication: 2017 Nov 28 (Print Publication: 2017).
DOI:	10.1128/MCB.00328-17
Abstrakt:	TP53 is one of the most commonly mutated genes in human cancers. Unlike other tumor suppressors that are frequently deleted or acquire loss-of-function mutations, the majority of TP53 mutations in tumors are missense substitutions, which lead to the expression of full-length mutant proteins that accumulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic events. Recently, mutant p53 proteins have been shown to mediate metabolic changes as a novel GOF to promote tumor development. There is a strong rationale that the GOF activities, including alterations in cellular metabolism, might vary between the different p53 mutants. Accordingly, the effect of different mutant p53 proteins on cancer cell metabolism is largely unknown. In this study, we have metabolically profiled several individual frequently occurring p53 mutants in cancers, focusing on glycolytic and mitochondrial oxidative phosphorylation pathways. Our investigation highlights the diversity of different p53 mutants in terms of their effect on metabolism, which might provide a foundation for the development of more effective targeted pharmacological approaches toward variants of mutant p53. (Copyright © 2017 American Society for Microbiology.)
Databáze:	MEDLINE
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