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 |
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| Authors: | Armstrong Michaele J Stang Michael T Liu Ye Gao Jinbo Ren Baoguo Zuckerbraun Brian S Mahidhara Raja S Xing Quanhua Pizzoferrato Eva Yim John H |
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| Institution: | Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA. |
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| 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. |
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| Keywords: | IRF-1 Survivin p21 Cell cycle Cancer |
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