PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation

Nat Cell Biol. 2007 Aug;9(8):932-44. doi: 10.1038/ncb1618. Epub 2007 Jul 22.


The serine/threonine kinase human Pim1 (hereafter PIM1) cooperates with human c-Myc (hereafter MYC) in cell cycle progression and tumorigenesis. However, the nature of this cooperation is still unknown. Here we show that, after stimulation with growth factor, PIM1 forms a complex with the dimer of MYC with MAX (Myc-associated factor X) via the MYC BoxII (MBII) domain. MYC recruits PIM1 to the E boxes of the MYC-target genes FOSL1 (FRA-1) and ID2, and PIM1 phosphorylates serine 10 of histone H3 (H3S10) on the nucleosome at the MYC-binding sites, contributing to their transcriptional activation. MYC and PIM1 colocalize at sites of active transcription, and expression profile analysis revealed that PIM1 contributes to the regulation of 20% of the MYC-regulated genes. Moreover, PIM1-dependent H3S10 phosphorylation contributes to MYC transforming capacity. These results establish a new function for PIM1 as a MYC cofactor that phosphorylates the chromatin at MYC-target loci and suggest that nucleosome phosphorylation, at E boxes, contributes to MYC-dependent transcriptional activation and cellular transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Chromatin / metabolism
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Multiprotein Complexes
  • Nucleosomes / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Proto-Oncogene Proteins c-pim-1 / metabolism*
  • Serine / metabolism*
  • Transcriptional Activation*
  • Vascular Endothelial Growth Factor A / metabolism


  • Chromatin
  • Histones
  • Multiprotein Complexes
  • Nucleosomes
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-myc
  • Vascular Endothelial Growth Factor A
  • fos-related antigen 1
  • Serine
  • PIM1 protein, human
  • Proto-Oncogene Proteins c-pim-1