ATM dependent apoptosis in the nervous system
ATM dependent apoptosis in the nervous system
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DOI：
10.1023/a:1009637512917
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发表时间：
2000-12-01
期刊：
影响因子：
7.2
通讯作者：
McKinnon, PJ
中科院分区：
文献类型：
--
作者：
Lee, Y;McKinnon, PJ
共济失调毛细血管扩张症是一种由 ATM 蛋白激酶突变引起的人类综合征，其特征是辐射敏感性和神经变性。尽管具有神经保护作用，但 ATM 在神经系统中功能的分子细节尚不确定。然而，在小鼠中，Atm对于电离辐射诱导的神经系统发育中的有丝分裂后群体的细胞凋亡至关重要。神经系统中 Atm 依赖性细胞凋亡也需要 p53，这与 p53 作为 ATM 主要底物的既定联系一致。此外，大多数（但不是全部）Atm 依赖性细胞凋亡也需要促凋亡效应子 Bax。因此，在发育中的神经系统中 DNA 受损后，Atm 在分化的神经细胞中启动 p53 依赖性凋亡级联反应。总之，这些数据表明 ATM 依赖性细胞凋亡对于消除在发育过程中积累的基因组损伤的神经细胞可能很重要，从而防止这些细胞在以后的生活中出现功能障碍。
Ataxia-telangiectasia is a human syndrome resulting from mutations of the ATM protein kinase that is characterized by radiation sensitivity and neurodegeneration. Although neuroprotective, the molecular details of ATM function in the nervous system are uncertain. However, in the mouse, Atm is essential for ionizing radiation-induced apoptosis in select postmitotic populations of the developing nervous system. Atm-dependent apoptosis in the nervous system also requires p53, consistent with the well-established link of p53 as a major substrate of ATM. Furthermore, the proapoptotic effector Bax is also required for most, but not all, Atm-dependent apoptosis. Therefore, after DNA damage in the developing nervous system, Atm initiates a p53-dependent apoptotic cascade in differentiating neural cells. Together, these data suggest ATM-dependent apoptosis may be important for elimination of neural cells that have accumulated genomic damage during development, thus preventing dysfunction of these cells later in life.