Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
Cancer Lett. 2012 Jun 1;319(1):56-65. doi: 10.1016/j.canlet.2011.12.027. Epub 2011 Dec 23.
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.
我们已经表明，干扰素调节因子 1（IRF-1）的异位表达导致人类癌细胞死亡，同时下调凋亡蛋白抑制剂（IAP）survivin 并诱导细胞周期依赖性激酶抑制剂 p21（WAF1/CIP1）。在本报告中，我们研究了 p21 在抑制 survivin 中的直接作用。我们表明，IRF-1 下调细胞周期蛋白 B1、cdc-2、细胞周期蛋白 E、E2F1、Cdk2、Cdk4，并导致 p21 介导的 G1 细胞周期停滞。有趣的是，虽然 p21 直接介导 G1 细胞周期停滞，但 IRF-1 或其他 IRF-1 信号通路可能直接调节人类癌细胞中的 survivin。
