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Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4

Inken Wierstra1, Jürgen Alves

  • 1Institute of Molecular Biology, Medical School Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. iwiwiwi@web.de

Biological Chemistry
|August 18, 2006
PubMed

Insights

The cell cycle regulator FOXM1c is normally inactive but is activated by cyclin D1/Cdk4. This activation is crucial for stimulating the G1/S-transition, promoting cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • FOXM1c (MPP2) is a proliferation-stimulating transactivator.
  • FOXM1c activity is regulated by RB, cyclin D1/Cdk4, and its own inhibitory domains.

Purpose of the Study:

  • To elucidate the regulatory mechanism of FOXM1c activation by cyclin D1/Cdk4.

Main Methods:

  • Investigated protein-protein interactions between FOXM1c, RB, and cyclin D1/Cdk4.
  • Assessed the impact of cyclin D1/Cdk4 on FOXM1c activity and its regulatory domains.

Main Results:

  • RB binds to FOXM1c's central domain, repressing its transactivation.
  • Cyclin D1/Cdk4 phosphorylates RB, disrupting the RB-FOXM1c interaction and releasing repression.
  • Cyclin D1/Cdk4 also relieves inhibition by FOXM1c's N-terminus, strongly activating FOXM1c in G1-phase.

Conclusions:

  • Cyclin D1/Cdk4 converts inactive FOXM1c into a potent transactivator during G1-phase.
  • This activation is essential for driving the G1/S-transition and cell proliferation.

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