title: Nuclear PKM2 regulates the Warburg effect.
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.
authors.affiliation: Brain Tumor Center; Department of Neuro-Oncology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D059447:Cell Cycle Checkpoints; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D006019:Glycolysis; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; D011770:Pyruvate Kinase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK; PKM1; PKM2; c-Myc; cyclin D1; histone; the Warburg effect