The c-Jun N-terminal kinase JNK functions upstream of Aurora B to promote entry into mitosis

Cell Cycle. 2008 Feb 15;7(4):533-41. doi: 10.4161/cc.7.4.5660.

Abstract

Mitogen-activated protein kinases (MAPKs) are components of signaling cascades regulated by environmental stimuli. In addition to participating in the stress response, the MAPKs c-Jun N-terminal Kinases JNK1 and JNK2 regulate the proliferation of normal and neoplastic cells. JNKs contribute to these processes largely by phosphorylating c-Jun and thus contributing to the activation of the AP-1 complex. We here report that JNKs control entry into mitosis. We have observed that JNK activity and phosphorylation of c-Jun become elevated during the G2/M transition of the cell cycle in immortalized fibroblasts and ovarian granulosa cells. Pharmacological inhibition of JNK causes a profound cell cycle arrest at the G2/M transition in both cell types. This effect is specific as it occurs with two distinct small molecule compounds. Inactivation of JNK prior to mitosis prevents expression of Aurora B and phosphorylation of Histone-H3 at Ser 10. Silencing of JNK1 and 2 causes a similar effect, whereas overexpression of JNK1 and 2 causes the opposite effect. Inhibition of JNK delays activation of cdc-2 and prevents downregulation of Cyclin B1. We conclude that JNK signaling promotes entry into mitosis by promoting expression of Aurora B and thereby phosphorylation of Histone-H3.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Bromodeoxyuridine
  • Female
  • Flow Cytometry
  • G2 Phase / physiology*
  • Gene Expression Regulation / physiology*
  • Granulosa Cells
  • Histones / metabolism
  • Immunoblotting
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mice
  • Mitosis / physiology*
  • NIH 3T3 Cells
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Signal Transduction / physiology*

Substances

  • Histones
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Bromodeoxyuridine