Nuclear PKM2 regulates the Warburg effect

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Checkpoints
  • Cell Nucleus / metabolism*
  • Cyclin D1 / metabolism
  • Glycolysis
  • HEK293 Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / metabolism
  • Pyruvate Kinase / metabolism*
  • Up-Regulation


  • Histones
  • Proto-Oncogene Proteins c-myc
  • Cyclin D1
  • Pyruvate Kinase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3