Chène Patrick, Fuchs Jean, Carena Ilaria, Furet Pascal, García-Echeverría Carlos
Oncology Department, Novartis K125 442, CH-4002 Basel, Switzerland.
FEBS Lett. 2002 Oct 9;529(2-3):293-7. doi: 10.1016/s0014-5793(02)03362-8.
Inhibitors of the p53-hdm2 interaction are attractive molecules for stimulating the p53 pathway in tumors. In this report, an inhibitor of the p53-hdm2 interaction, the AP peptide, is used to activate p53 in tumor cells expressing various levels of hdm2 protein. It induces apoptosis only in cells expressing high endogenous levels of hdm2 protein. The absence of apoptosis in tumor cells with low hdm2 levels is due not to alterations in the p53-dependent apoptotic pathway but to a different regulation of this pathway. The peptide is also less toxic for non-tumor cells than for tumor cells overexpressing the hdm2 protein.
p53-hdm2相互作用的抑制剂是刺激肿瘤中p53信号通路的有吸引力的分子。在本报告中，一种p53-hdm2相互作用的抑制剂，即AP肽，被用于激活表达不同水平hdm2蛋白的肿瘤细胞中的p53。它仅在高内源性hdm2蛋白表达的细胞中诱导凋亡。hdm2水平低的肿瘤细胞中不存在凋亡，这不是由于p53依赖性凋亡途径的改变，而是由于该途径的不同调节。该肽对非肿瘤细胞的毒性也低于对过表达hdm2蛋白的肿瘤细胞的毒性。
