Drosophila p53 is a structural and functional homolog of the tumor suppressor p53
Drosophila p53 is a structural and functional homolog of the tumor suppressor p53
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DOI：
10.1016/s0092-8674(00)80626-1
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发表时间：
2000-03-31
期刊：
影响因子：
64.5
通讯作者：
Kopczynski, C
中科院分区：
文献类型：
--
作者：
Ollmann, M;Young, LM;Kopczynski, C
p53在癌发生中的重要性源于其在响应细胞应激诱导细胞周期停滞或凋亡中的中心作用。我们已经鉴定出p53的果蝇同源物（“Dmp 53”）。与哺乳动物p53类似，Dmp53特异性结合人p53结合位点，并且Dmp53的过表达诱导细胞凋亡。重要的是，Dmp53功能的抑制使细胞对X射线诱导的凋亡具有抗性，这表明Dmp53是DNA损伤的凋亡反应所必需的。与哺乳动物p53不同，Dmp53在过表达时似乎不能诱导G1期细胞周期阻滞，并且抑制Dmp53活性不影响X射线诱导的细胞周期停滞。这些数据揭示了p53的祖先的促凋亡功能，并确定果蝇作为一个理想的模型系统，用于阐明DNA损伤诱导的p53凋亡途径。
The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses. We have identified a Drosophila homolog of p53 ("Dmp53"). Like mammalian p53, Dmp53 binds specifically to human p53 binding sites, and overexpression of Dmp53 induces apoptosis. Importantly, inhibition of Dmp53 function renders cells resistant to X ray-induced apoptosis, suggesting that Dmp53 is required for the apoptotic response to DNA damage. Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest. These data reveal an ancestral proapoptotic function for p53 and identify Drosophila as an ideal model system for elucidating the p53 apoptotic pathway(s) induced by DNA damage.