Basal c-Jun N-terminal kinases promote mitotic progression through histone H3 phosphorylation

Cell Cycle. 2008 Jan 15;7(2):216-21. doi: 10.4161/cc.7.2.5155. Epub 2007 Oct 11.

Abstract

Phosphorylation of histone H3 at serine 10 (S10) is essential for the onset of mitosis. Here, we show that basal c-Jun N-terminal kinases (JNKs) are required for mitotic histone H3-S10 phosphorylation in human primary fibroblast IMR90 cells. Inhibition of JNKs by specific pharmacologic inhibitors, expression of dominant-negative JNK1 and 2 mutants, or RNAi of JNK1 and 2 prevented phosphorylation of histone H3 at S10 in vivo. The JNK-specific inhibitor SP600125 blocked mitotic entry, as shown by its ability to prevent CDK1 dephosphorylation and cyclin A degradation. Basal JNK phosphorylation increased at G(2)/M phase, although total JNK protein levels remained unchanged. In addition, basal JNKs were localized in nuclei and centrosomes during this time, suggesting that the nuclear localization of JNKs during G(2)/M is tightly coupled with histone H3 phosphorylation. Basal JNKs were able to phosphorylate histone H3 in vitro and coprecipitation of histone H3 and JNKs was only detected at G(2)/M. Taken together, these data strongly suggest that basal JNKs play a key role in controlling histone H3 phosphorylation for mitotic entry at G(2)/M phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Cell Culture Techniques
  • Cell Cycle
  • Cell Line
  • Cell Proliferation
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Histones / metabolism*
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Mitosis*
  • NIH 3T3 Cells
  • Phosphorylation

Substances

  • Anthracenes
  • Enzyme Inhibitors
  • Histones
  • pyrazolanthrone
  • Mitogen-Activated Protein Kinase 8