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p65 Negatively regulates transcription of the cyclin E gene

Vaibhao C Janbandhu1, Anup K Singh, Atish Mukherji

  • 1Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.

The Journal of Biological Chemistry
|April 14, 2010
PubMed

Insights

Nuclear factor-kappa B (NF-kappaB) acts as a cell cycle brake. This study shows NF-kappaB represses cyclin E gene transcription, leading to cell cycle arrest at G1/S phase.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Nuclear factor-kappa B (NF-kappaB) is crucial for cellular functions, including cell cycle regulation.
  • NF-kappaB activates cyclin D1 and p21(Waf1) genes, suggesting a role in cell cycle modulation.

Purpose of the Study:

  • To investigate the role of NF-kappaB in G1/S phase regulation.
  • To identify NF-kappaB's transcriptional targets involved in cell cycle progression.

Main Methods:

  • Overexpression of NF-kappaB and induction by tumor necrosis factor-alpha.
  • Monitoring transcriptional regulators and gene expression.
  • Chromatin immunoprecipitation and PCR-based assays to analyze promoter binding and chromatin structure.

Main Results:

  • Cyclin E gene identified as a key transcriptional target of NF-kappaB.
  • NF-kappaB recruitment to the cyclin E promoter correlated with gene transrepression.
  • NF-kappaB induction led to decreased cyclin E transcription, inactive cyclin E-cdk2 complexes, and G1/S phase arrest.

Conclusions:

  • NF-kappaB acts as a negative regulator of the cell cycle.
  • Transcriptional repression of cyclin E by NF-kappaB is a mechanism for cell cycle arrest.

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