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.
Michaele J Armstrong  1 ,  Michael T Stang ,  Ye Liu ,  Jinbo Gao ,  Baoguo Ren ,  Brian S Zuckerbraun ,  Raja S Mahidhara ,  Quanhua Xing ,  Eva Pizzoferrato ,  John H Yim
Affiliations
  • 1. Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
PMID: 22200613 DOI: 10.1016/j.canlet.2011.12.027
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.