ATM 蛋白激酶：细胞应激防御的关键。
ATM protein kinase: the linchpin of cellular defenses to stress.
机构信息
Institute of Molecular Biology and Biotechnology, The University of Lahore, 1 Km Raiwind Road, Thokar Niaz Baig, Lahore, Pakistan.
出版信息
Cell Mol Life Sci. 2011 Sep;68(18):2977-3006. doi: 10.1007/s00018-011-0683-9. Epub 2011 May 2.
Abstract
ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.
摘要
ATM 是参与监测细胞基因组完整性的最重要的分子。任何对 DNA 的损伤都会无情地挑战细胞机制，使其参与识别、处理和修复这些损伤。ATM 激酶被早期激活，以检测和信号 DNA 中的损伤，使细胞周期停滞，建立 DNA 修复信号，并忠实地修复受损的染色质。ATM 的激活在肿瘤发生、代谢综合征和神经退行性变的障碍中起着重要的作用。因此，通过开发能够调节细胞对应激的反应的新疗法，研究 ATM 依赖性 DNA 损伤信号通路有望治疗多种使人衰弱的疾病。在这篇综述中，我们试图解开 ATM 信号通路的复杂网络，以确定 ATM 下的多种作用，这些作用是在 AT 患者观察到的复杂表型的基础上。
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