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.
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.
Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
Michaele J
MJ
Armstrong
Michael T
MT
Stang
Ye
Y
Liu
Jinbo
J
Gao
Baoguo
B
Ren
Brian S
BS
Zuckerbraun
Raja S
RS
Mahidhara
Quanhua
Q
Xing
Eva
E
Pizzoferrato
John H
JH
Yim
D059447:Cell Cycle Checkpoints / Q000502:physiology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D050856:Interferon Regulatory Factor-1; D009363:Neoplasm Proteins; D000077022:Survivin