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Autophosphorylation and ATM activation: additional sites add to the complexity.自身磷酸化和 ATM 激活:更多的位点增加了复杂性。
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Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites.丝氨酸 1981 处的自身磷酸化稳定了 DNA 损伤部位的 ATM。
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Ataxia telangiectasia-mutated (ATM) kinase activity is regulated by ATP-driven conformational changes in the Mre11/Rad50/Nbs1 (MRN) complex.共济失调毛细血管扩张症突变(ATM)激酶活性受 Mre11/Rad50/Nbs1(MRN)复合物中 ATP 驱动的构象变化调节。
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本文引用的文献

1
Therapeutic Effect of Epigallocatechin-3-gallate (EGCG) and Silibinin on ATM Dynamics in Prostate Cancer Cell Line LNCaP.表没食子儿茶素-3-没食子酸酯(EGCG)和水飞蓟宾对前列腺癌细胞系LNCaP中共济失调毛细血管扩张突变蛋白(ATM)动力学的治疗作用
World J Oncol. 2010 Dec;1(6):242-246. doi: 10.4021/wjon248w. Epub 2011 Jan 1.
2
ATM activation in the presence of oxidative stress.在氧化应激存在的情况下激活 ATM。
Cell Cycle. 2010 Dec 15;9(24):4805-11. doi: 10.4161/cc.9.24.14323.
3
Autophosphorylation and ATM activation: additional sites add to the complexity.自身磷酸化和 ATM 激活:更多的位点增加了复杂性。
J Biol Chem. 2011 Mar 18;286(11):9107-19. doi: 10.1074/jbc.M110.204065. Epub 2010 Dec 13.
4
ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage.DNA 损伤后核磷酸蛋白质组的 ATM 依赖性和非依赖性动态变化。
Sci Signal. 2010 Dec 7;3(151):rs3. doi: 10.1126/scisignal.2001034.
5
mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1α.在缺氧条件下,mTORC1 信号受 ATM 依赖性磷酸化 HIF-1α的控制。
Mol Cell. 2010 Nov 24;40(4):509-20. doi: 10.1016/j.molcel.2010.10.030.
6
ATM activation by oxidative stress.氧化应激激活 ATM。
Science. 2010 Oct 22;330(6003):517-21. doi: 10.1126/science.1192912.
7
A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation.细胞质 ATM-TRAF6-cIAP1 模块将核 DNA 损伤信号与泛素介导的 NF-κB 激活联系起来。
Mol Cell. 2010 Oct 8;40(1):63-74. doi: 10.1016/j.molcel.2010.09.008.
8
The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress.ZFHX3(ATBF1)转录因子诱导 PDGFRB,后者在细胞质中激活 ATM 以保护小脑神经元免受氧化应激。
Dis Model Mech. 2010 Nov-Dec;3(11-12):752-62. doi: 10.1242/dmm.004689. Epub 2010 Sep 27.
9
CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.CK2 磷酸化依赖性 R2TP 复合物与 TEL2 的结合对于 mTOR 和 SMG1 的稳定性至关重要。
Mol Cell. 2010 Sep 24;39(6):839-50. doi: 10.1016/j.molcel.2010.08.037.
10
Epigenetic modifications in double-strand break DNA damage signaling and repair.双链断裂 DNA 损伤信号转导和修复中的表观遗传修饰。
Clin Cancer Res. 2010 Sep 15;16(18):4543-52. doi: 10.1158/1078-0432.CCR-10-0513. Epub 2010 Sep 7.

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.

DOI:10.1007/s00018-011-0683-9
PMID:21533982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11115042/
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。