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Cell Cycle. 2013 Oct 1;12(19):3154-8. doi: 10.4161/cc.26182. Epub 2013 Aug 26.

Nuclear PKM2 regulates the Warburg effect.

Author information

1
Brain Tumor Center; Department of Neuro-Oncology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.

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.

KEYWORDS:

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

PMID:
24013426
PMCID:
PMC3865010
DOI:
10.4161/cc.26182
[Indexed for MEDLINE]
Free PMC Article

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