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FoxM1 regulates growth factor-induced expression of kinase-interacting stathmin (KIS) to promote cell cycle

Vladimir Petrovic1, Robert H Costa1, Lester F Lau1

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607.

The Journal of Biological Chemistry
|November 7, 2007
PubMed

Insights

The Forkhead box M1 (FoxM1) transcription factor controls cell division by regulating p27(Kip1) levels. FoxM1 down-regulates p27(Kip1) through multiple pathways, promoting cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Forkhead box M1 (FoxM1) is a key transcription factor regulating cell cycle progression and mitosis.
  • FoxM1 influences p27(Kip1) degradation via Skp2 and Cks1, components of the SCF ubiquitin ligase complex.
  • Kinase-interacting stathmin (KIS) regulates cell cycle by phosphorylating p27(Kip1), affecting its nuclear localization.

Purpose of the Study:

  • To elucidate additional mechanisms of FoxM1-mediated regulation of p27(Kip1).
  • To investigate the role of FoxM1 in regulating growth factor-induced expression of KIS.
  • To understand how FoxM1 impacts p27(Kip1) nuclear accumulation.

Main Methods:

  • Utilized cell models with FoxM1 deletion or FoxM1-short interfering RNA (siRNA).
  • Assessed KIS expression levels in response to FoxM1 manipulation.
  • Investigated KIS as a direct transcriptional target of FoxM1.

Main Results:

  • Impaired KIS expression observed in cells lacking functional FoxM1.
  • FoxM1 deletion or knockdown led to p27(Kip1) accumulation in the nucleus.
  • Demonstrated that KIS is a direct transcriptional target of FoxM1.

Conclusions:

  • FoxM1 promotes cell cycle progression by down-regulating p27(Kip1) through multiple mechanisms.
  • FoxM1 regulates KIS expression, contributing to p27(Kip1) control.
  • These findings reveal a novel pathway for FoxM1 in cell cycle regulation.

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