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Regulation of aurora B expression by the bromodomain protein Brd4

Jianxin You1, Qing Li, Chong Wu

  • 1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Molecular and Cellular Biology
|July 15, 2009
PubMed

Insights

Bromodomain protein Brd4 is crucial for cell cycle progression. Brd4 controls the transcription of Aurora B kinase, essential for chromosome segregation and cytokinesis, preventing mitotic errors.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Bromodomain protein Brd4 is implicated in cellular proliferation and cell cycle regulation.
  • Aberrant cell cycle control is a hallmark of cancer.

Purpose of the Study:

  • To investigate the role of Brd4 in cell cycle regulation.
  • To determine the relationship between Brd4 and Aurora B kinase expression and function.

Main Methods:

  • RNA interference (RNAi) to knockdown Brd4 in cancer cells and primary keratinocytes.
  • Analysis of chromosome segregation and cytokinesis.
  • Measurement of Aurora B protein and transcript levels.
  • Aurora B promoter reporter assays.
  • Exogenous Brd4 expression studies.

Main Results:

  • Brd4 knockdown led to aberrant chromosome segregation and failed cytokinesis.
  • Suppression of Brd4 decreased Aurora B levels and abolished its chromosomal localization.
  • Exogenous Brd4 stimulated Aurora B transcription and upregulated its expression.
  • Altered Brd4 levels mimicked the effects of Aurora B inactivation or overexpression, causing mitotic catastrophe and multinucleation.

Conclusions:

  • Brd4 is essential for maintaining cell cycle progression.
  • Brd4 regulates cell cycle progression partly by controlling Aurora B kinase transcription.
  • Brd4's role in Aurora B regulation is critical for proper chromosome segregation and cytokinesis.

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