DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes
DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes
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DOI：
10.1016/s1097-2765(02)00431-8
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发表时间：
2002-01-01
期刊：
影响因子：
16
通讯作者：
Levrero, M
中科院分区：
文献类型：
--
作者：
Costanzo, A;Merlo, P;Levrero, M
肿瘤抑制因子p53及其近亲p73在DNA损伤导致细胞周期阻滞或细胞凋亡时被激活。在这里，我们发现DNA损伤通过乙酰转移酶p300诱导p73的乙酰化。在p53（-/-）背景下，抑制p300的酶活性会阻碍细胞凋亡。此外，不可乙酰化的p73在激活促凋亡p53AIP1基因的转录方面存在缺陷，但保留了调节其他靶标（如p21）的完整能力。最后，p300介导的p73乙酰化需要原癌基因c-abl。我们的研究结果表明，DNA损伤诱导的乙酰化通过增强p73选择性激活促凋亡靶基因转录的能力来增强p73的凋亡功能。
The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53(-/-) background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes.