Interferon Regulatory Factor 1 (IRF-1) induces p21(WAF1/CIP1) dependent cell cycle arrest and p21(WAF1/CIP1) independent modulation of survivin in cancer cells

Cancer Lett. 2012 Jun 1;319(1):56-65. doi: 10.1016/j.canlet.2011.12.027. Epub 2011 Dec 23.

Abstract

We have shown that the ectopic expression of Interferon Regulatory Factor 1 (IRF-1) results in human cancer cell death accompanied by the down-regulation of the Inhibitor of Apoptosis Protein (IAP) survivin and the induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1). In this report, we investigated the direct role of p21 in the suppression of survivin. We show that IRF-1 down-regulates cyclin B1, cdc-2, cyclin E, E2F1, Cdk2, Cdk4, and results in p21-mediated G1 cell cycle arrest. Interestingly, while p21 directly mediates G1 cell cycle arrest, IRF-1 or other IRF-1 signaling pathways may directly regulate survivin in human cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Checkpoints / physiology*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Down-Regulation
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Interferon Regulatory Factor-1 / metabolism*
  • Neoplasm Proteins / metabolism*
  • Survivin

Substances

  • BIRC5 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Inhibitor of Apoptosis Proteins
  • Interferon Regulatory Factor-1
  • Neoplasm Proteins
  • Survivin