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Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity

J L Siegert1, J J Rushton, W R Sellers

  • 1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.

Oncogene
|December 29, 2000
PubMed

Insights

Cyclin D1 blocks retinoblastoma protein (Rb) inhibition of TAFII250 kinase activity. This suggests cyclin D1 independently regulates Rb activity by interacting with TAFII250, not Rb.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Tumor Suppressor Proteins

Background:

  • Retinoblastoma protein (Rb) inhibits TAFII250 kinase activity.
  • Cyclin D1 binds to TAFII250 near the Rb-binding site.

Purpose of the Study:

  • Investigate if cyclin D1 affects the Rb-TAFII250 interaction.
  • Determine the mechanism by which cyclin D1 influences TAFII250 kinase activity.

Main Methods:

  • In vitro kinase assays.
  • Coincubation of Rb, cyclin D1, and TAFII250.
  • Use of Rb mutants and adenovirus E1A protein.

Main Results:

  • Cyclin D1 blocks Rb-mediated inhibition of TAFII250 kinase activity.
  • Cyclin D1 does not affect TAFII250 kinase activity alone.
  • p107 inhibition of TAFII250 is also alleviated by cyclin D1.
  • Cyclin D1 acts via TAFII250, not Rb, and does not compete with Rb for binding.
  • Adenovirus E1A protein mimics cyclin D1's effect.

Conclusions:

  • Cyclin D1 regulates Rb activity through TAFII250.
  • Cyclin D1 may independently modulate Rb function.
  • This interaction offers a novel regulatory mechanism for Rb activity.

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