Literature DB >> 24013426

Nuclear PKM2 regulates the Warburg effect.

Weiwei Yang1, Zhimin Lu.   

Abstract

Pyruvate kinase is a rate-limiting glycolytic enzyme. The PKM1 and PKM2 isoforms result from mutually exclusive alternative splicing of the PKM pre-mRNA. PKM2 rather than PKM1 regulates the Warburg effect and tumorigenesis by poorly understood mechanisms. Emerging evidence has revealed that ERK1/2 phosphorylates PKM2, but not PKM1, leading to PIN1-dependent cis-trans isomerization and conversion of PKM2 from a tetramer to a monomer. Monomeric PKM2 translocates into the nucleus, where it functions as a histone kinase and upregulates the expression of c-Myc and cyclin D1, thereby promoting the Warburg effect and cell cycle progression, respectively. Thus, nuclear PKM2 is essential for tumorigenesis and may serve as a target for treating human cancer.

Entities:  

Keywords:  ERK; PKM1; PKM2; c-Myc; cyclin D1; histone; the Warburg effect

Mesh：

Substances：

Year:  2013        PMID： 24013426      PMCID： PMC3865010          DOI： 10.4161/cc.26182

Source DB:  PubMed          Journal:  Cell Cycle        ISSN： 1551-4005            Impact factor:   4.534


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