2020年3月6日 · ATM是多个信号级联的关键调控因子，它对破坏性的IR(电离辐射)、辐射剂或正常过程引起的DNA链断裂做出响应。 这些反应包括激活细胞周期Chk因子 (检查点因子)、DNA修复和凋亡。 此外，ATM似乎是一个“看护者”，抑制特定T细胞谱系的肿瘤发生。 其下游靶点包括Chk1(细胞周期检查点激酶-1)，Chk2(细胞周期检查点激酶-2)，肿瘤抑制因子如p53和BRCA(乳腺癌)，DNA修复因子如Rad50、Rad51、GADD45(生长停滞和DNA损伤诱导)，以及其他信号分 …

In addition, suppressing DNA damage and replication checkpoint responses by inhibiting Chk1 can enhance tumor cell killing by diverse genotoxic agents. Here, we review current understanding of the organization and functions of the ATM-Chk2 and ATR-Chk1 pathways and the prospects for targeting DNA damage signaling processes for therapeutic purposes.

ATM (Ataxia-telangiectasia mutated proteins) 是一种丝氨酸-苏氨酸蛋白激酶，是 DNA 损伤应答 (DDR) 的关键调节因子。 ATM 是位名副其实的“指挥官”，在 DNA 双链断裂 (DSB) 中，参与细胞周期检查点维护、DNA 损伤修复和端粒维护等，在调节细胞对 DNA 损伤的反应中发挥重要 ...

dna 损伤会通过 atm/atr 和 chk1/2 激酶激活反应通路来限制 cdk 活性，从而导致细胞周期停滞和 dna 修复或细胞死亡。 G2/M 检查点可防止带有受损 DNA 的细胞进入有丝分裂 (M) 阶段。

2001年4月12日 · Here we report a functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) 12 and Cdc25A, and implicate this mechanism in controlling the S-phase checkpoint. We show that...

近期，中国医科大学曹流教授团队在Cell Death Differ杂志上发表题为SIRT1 modulates cell cycle progression through regulating CHK2 acetylation-phosphorylation的研究成果，探索了SIRT1对DNA损伤修复反应途径因子的功能调控规律，揭示了SIRT1通过去乙酰化修饰，影响CHK2磷酸化，从而在维持基因组稳定性中发挥重要作用【10】。 DNA损伤、代谢应激等刺激导致ROS累积和氧化应激损伤。

2010年1月1日 · Here, we review current understanding of the organization and functions of the ATM–Chk2 and ATR–Chk1 pathways and the prospects for targeting DNA damage signaling processes for therapeutic purposes. Cells in multicellular organisms are continuously exposed to DNA damage arising from a variety of endogenous and exogenous sources.

2023年3月6日 · We aligned the amino acid sequences of ATM family proteins and found a conserved CHK-2 consensus phosphorylation motif (R-X-X-S/T) within their FAT domains, which are critical for ATM/ATR ...

Herein, we review the inhibitors of five of the key regulators of the cell cycle checkpoints in cancer cells and in the particular settings of cancer stem cells: ATM and ATR, kinases that play apical roles in DDR; CHK1 and CHK2 kinases, respectively activated by ATR and ATM, that are central transducers towards cell cycle arrest, DNA repair and ...

2020年5月18日 · Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress.