Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.
Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.
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DOI：
10.1101/gad.8.23.2817
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发表时间：
1994-12
影响因子：
10.5
通讯作者：
A. Wagner;J. Kokontis;N. Hay
中科院分区：
文献类型：
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作者：
A. Wagner;J. Kokontis;N. Hay
c-myc原癌基因的表达失调可在某些生理条件下导致细胞凋亡。通过将条件活性Myc等位基因引入p53无效的原代胚胎成纤维细胞，以及没有内源性p53表达但异位表达温度敏感性p53等位基因的成纤维细胞，我们表明野生型p53的表达是Myc介导的细胞凋亡易感性所必需的。虽然异位表达野生型p53阻断细胞在G1期的细胞周期，G1期阻滞异亮氨酸饥饿，在一种独立的方式p53，并没有赋予细胞凋亡的敏感性。因此，生长停滞本身不足以诱导Myc介导的细胞凋亡;相反，p53固有的特性是特别需要的。此外，凋亡不需要诱导p53靶蛋白，包括细胞周期蛋白依赖性激酶抑制剂p21 waf 1/cip 1。因此，p53在细胞凋亡中的作用可能不同于其在细胞周期阻滞中的作用。
Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 allele, we show that expression of wild-type p53 is required for susceptibility to Myc-mediated apoptosis. Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis. Thus, growth arrest per se is not sufficient to induce Myc-mediated apoptosis; instead, a property intrinsic to p53 is specifically required. Moreover, apoptosis did not require induction of p53 target proteins, including the cyclin-dependent kinase inhibitor p21waf1/cip1. Therefore, the role of p53 in apoptosis may be distinct from its role in cell cycle arrest.