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Regulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling pathway

Kelly Cude1, Yupeng Wang, Hyun-Jung Choi

  • 1Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA.

The Journal of Cell Biology
|April 25, 2007
PubMed

Insights

A novel signaling pathway involving extracellular signal-regulated kinase 5 (ERK5) and nuclear factor kappaB (NFkappaB) is crucial for cell cycle progression through the G2-M phases, impacting mitosis and gene transcription.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Biology

Background:

  • Cell cycle regulation is vital for cell and cancer biology.
  • G1-S phase regulation is well-studied, but G2-M phase mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the role of extracellular signal-regulated kinase 5 (ERK5) in G2-M phase cell cycle progression.
  • To identify signaling pathways downstream of ERK5 that regulate mitosis.

Main Methods:

  • Utilized cell cycle analysis to study G2-M progression.
  • Investigated the activation of nuclear factor kappaB (NFkappaB) by ERK5.
  • Examined the impact of NFkappaB inhibition on G2-M specific gene expression and mitotic entry.

Main Results:

  • Extracellular signal-regulated kinase 5 (ERK5) is activated during G2-M phases and is essential for timely mitotic entry.
  • ERK5 activation leads to nuclear factor kappaB (NFkappaB) activation via ribosomal S6 kinase 2 (RSK2).
  • Inhibition of NFkappaB at G2-M delays mitosis and suppresses transcription of key G2-M genes (e.g., cyclin B1, Plk-1).

Conclusions:

  • A novel ERK5-NFkappaB signaling pathway is identified as a key regulator of G2-M cell cycle progression.
  • This pathway links ERK5 activity to the transcriptional control of genes necessary for mitosis.
  • Understanding this pathway offers potential targets for cancer biology research.

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