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Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin

Jessy Cartier1, Jean Berthelet, Arthur Marivin

  • 1Institut National de la Santé et de la Recherche Médicale UMR866, Dijon, F-21079, France.

The Journal of Biological Chemistry
|June 10, 2011
PubMed

Insights

Cellular inhibitor of apoptosis protein-1 (cIAP1) regulates E2F1 transcription in the nucleus, impacting cell proliferation. This nuclear function differs from its known cytoplasmic roles in TNF and NF-κB signaling.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cellular inhibitor of apoptosis protein-1 (cIAP1) is primarily known for its cytoplasmic roles in regulating TNF receptor and NF-κB signaling pathways.
  • The nuclear localization and function of cIAP1 in certain cell types remain largely uncharacterized.

Purpose of the Study:

  • To investigate the nuclear function of cIAP1.
  • To determine if cIAP1 interacts with and regulates transcription factors involved in cell cycle progression.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • Reporter assays to measure transcriptional activity.
  • Chromatin immunoprecipitation (ChIP) to determine promoter occupancy.
  • siRNA-mediated gene silencing to evaluate functional consequences.

Main Results:

  • cIAP1 directly interacts with the DNA-binding domain of the E2F1 transcription factor.
  • cIAP1 significantly enhances E2F1 transcriptional activity on CCNE and synthetic promoters.
  • cIAP1 is recruited to E2F binding sites on CCNE and CCNA promoters in a cell cycle- and differentiation-dependent manner.
  • Silencing cIAP1 reduces E2F1 binding to DNA and inhibits E2F1-mediated transcription of CCNE.
  • Down-regulation of nuclear cIAP1 in HeLa, THP1, and primary human mammary epithelial cells decreases cyclin E and A expression and inhibits cell proliferation.

Conclusions:

  • Nuclear cIAP1 functions as a transcriptional co-activator for E2F1.
  • This novel nuclear role of cIAP1 in regulating E2F1 activity impacts cell cycle gene expression and proliferation.
  • The nuclear function of cIAP1 is distinct from its well-established cytoplasmic roles.

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