Poly(ADP-ribosyl)ation of p53 during apoptosis in human osteosarcoma cells.
Poly(ADP-ribosyl)ation of p53 during apoptosis in human osteosarcoma cells.
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发表时间：
1999-05
期刊：
影响因子：
11.2
通讯作者：
C. Simbulan-Rosenthal;D. Rosenthal;Ruibai Luo;M. Smulson
中科院分区：
文献类型：
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作者：
C. Simbulan-Rosenthal;D. Rosenthal;Ruibai Luo;M. Smulson
据观察，人骨肉瘤细胞的自发凋亡与细胞内 p53 丰度的显着增加有关。免疫沉淀和免疫印迹分析表明，p53 与多种其他核蛋白一起在这些细胞凋亡程序的早期经历了广泛的聚（ADP-核糖基）化。随后聚（ADP-核糖）（PAR）的降解（可能是由 PAR 糖水解酶（唯一报道的降解 PAR 的酶）附着在 p53 上）明显伴随着蛋白水解加工的开始和 caspase-3 的激活、caspase-3 介导的聚（ADP-核糖）聚合酶（PARP）的裂解以及细胞死亡后期的核小体间 DNA 断裂。与 p53 共价结合的 PAR 的减少也与 p53 反应基因 bax 和 Fas 表达的显着诱导相一致。这些结果表明，聚（ADP-核糖基）化可能在 p53 功能的调节中发挥作用，并暗示 PARP 和/或 PAR 在细胞凋亡早期的调节作用。
Spontaneous apoptosis in human osteosarcoma cells was observed to be associated with a marked increase in the intracellular abundance of p53. Immunoprecipitation and immunoblot analysis revealed that, together with a variety of other nuclear proteins, p53 undergoes extensive poly(ADP-ribosyl)ation early during the apoptotic program in these cells. Subsequent degradation of poly(ADP-ribose) (PAR), attached to p53 presumably by PAR glycohydrolase, the only reported enzyme to degrade PAR, was apparent concomitant with the onset of proteolytic processing and activation of caspase-3, caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP), and internucleosomal DNA fragmentation during the later stages of cell death. The decrease in PAR covalently bound to p53 also coincided with the marked induction of expression of the p53-responsive genes bax and Fas. These results suggest that poly(ADP-ribosyl)ation may play a role in the regulation of p53 function and implies a regulatory role for PARP and/or PAR early in apoptosis.