Bennett M, Macdonald K, Chan S W, Luzio J P, Simari R, Weissberg P
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
Science. 1998 Oct 9;282(5387):290-3. doi: 10.1126/science.282.5387.290.
p53 acts as a tumor suppressor by inducing both growth arrest and apoptosis. p53-induced apoptosis can occur without new RNA synthesis through an unknown mechanism. In human vascular smooth muscle cells, p53 activation transiently increased surface Fas (CD95) expression by transport from the Golgi complex. Golgi disruption blocked both p53-induced surface Fas expression and apoptosis. p53 also induced Fas-FADD binding and transiently sensitized cells to Fas-induced apoptosis. In contrast, lpr and gld fibroblasts were resistant to p53-induced apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic stores.
p53通过诱导生长停滞和细胞凋亡发挥肿瘤抑制作用。p53诱导的细胞凋亡可通过未知机制在无新RNA合成的情况下发生。在人血管平滑肌细胞中,p53激活通过从高尔基体复合体转运而短暂增加表面Fas(CD95)表达。高尔基体破坏阻断了p53诱导的表面Fas表达和细胞凋亡。p53还诱导Fas-FADD结合并使细胞短暂对Fas诱导的细胞凋亡敏感。相比之下,lpr和gld成纤维细胞对p53诱导的细胞凋亡具有抗性。因此,p53可通过从细胞质储存中转运Fas来介导细胞凋亡。