Gartenhaus R B, Wang P, Hoffmann P
Department of Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):265-8. doi: 10.1073/pnas.93.1.265.
The WAF1/CIP1 protein has been identified as a downstream mediator of the tumor suppressor p53 in regulating cell cycle progression through a G1-phase check-point. Recent work has implicated the functional status of p53 as a critical determinant in the apoptotic response of certain cell lines to DNA damaging agents. By using human T-cell leukemia virus type I-transformed lymphoid cell lines that differ in their level and function of wild-type p53, we investigated the induction of WAF1/CIP1 and apoptosis after exposure to Adriamycin, a genotoxic agent. We found that regardless of the p53 status in these cell lines, WAF1/CIP1 RNA was rapidly induced in response to Adriamycin treatment. An elevated level of WAF1/CIP1 protein was observed as well. Additionally, we demonstrated that apoptosis was induced in all cell lines analyzed despite some having functionally inactive p53 protein. Our data suggest that a p53-independent pathway may play a role in the apoptotic response observed in some cell lines after exposure to DNA damaging agents.
WAF1/CIP1蛋白已被确定为肿瘤抑制因子p53的下游介质，通过G1期检查点调节细胞周期进程。最近的研究表明，p53的功能状态是某些细胞系对DNA损伤剂凋亡反应的关键决定因素。通过使用野生型p53水平和功能不同的人I型T细胞白血病病毒转化的淋巴母细胞系，我们研究了暴露于遗传毒性剂阿霉素后WAF1/CIP1的诱导和凋亡情况。我们发现，无论这些细胞系中的p53状态如何，WAF1/CIP1 RNA都会在阿霉素处理后迅速被诱导。同时也观察到WAF1/CIP1蛋白水平升高。此外，我们证明，尽管有些细胞系的p53蛋白功能失活，但所有分析的细胞系均诱导了凋亡。我们的数据表明，p53非依赖性途径可能在某些细胞系暴露于DNA损伤剂后观察到的凋亡反应中起作用。
