Activation of p53 by oncogenes
Activation of p53 by oncogenes
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DOI：
10.1677/erc.0.0060045
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发表时间：
1999-03-01
影响因子：
3.9
通讯作者：
Lowe, SW
中科院分区：
文献类型：
--
作者：
Lowe, SW
p53被多种细胞应激激活，包括DNA损伤、缺氧和促有丝分裂癌基因，但每个信号与p53作为肿瘤抑制因子的结合程度仍不清楚。在非永生细胞中，腺病毒E1 A致癌基因激活p53以促进细胞凋亡，而致癌ras激活p53以促进细胞衰老。p53的失活防止E1 A诱导的细胞凋亡或Ras诱导的衰老，使增殖继续不减弱。在每种情况下，癌基因激活p53的能力涉及与其转化潜力所需的功能相同的功能，这意味着p53激活作为一种故障安全机制来对抗过度增殖信号。此外，p19（ARF）是癌基因信号传导至p53的严格要求。事实上，ARF -本身是一种肿瘤抑制因子-在这种反应中起着中介作用，这表明p53的肿瘤抑制活性可能源于其消除癌基因表达细胞的能力。
p53 is activated by a variety of cellular stresses, including DNA damage, hypoxia, and mitogenic oncogenes, but the extent to which each signal engages p53 as a tumour suppressor remains unknown. In non-immortal cells, the adenovirus E1A oncogene activates p53 to promote apoptosis, whereas oncogenic ras activates p53 to promote cellular senescence. Inactivation of p53 prevents E1A-induced apoptosis or Ras-induced senescence, allowing proliferation to continue unabated. In each instance, the ability of the oncogene to activate p53 involves the same functions as are required for their transforming potential, implying that p53 activation acts as a fail-safe mechanism to counter hyperproliferative signals. Furthermore, p19(ARF) is strictly required for oncogene signalling to p53. The fact that ARF - itself a tumour suppressor - acts as an intermediary in this response argues that the tumour suppressor activity of p53 can arise from its ability to eliminate oncogene-expressing cells.