摘要
毛细血管扩张共济失调突变基因(ataxia-telangiectasia mutated gene,ATM基因)变异导致遗传性毛细血管扩张共济失调症(ataxia-telangiectasia,A-T)。ATM基因编码产物———ATM蛋白激酶主要分布于增殖细胞核中。根据ATM蛋白激酶在细胞周期中作用底物如检测点激酶2(checkpoint kinase 2,Chk2)、奈梅亨断裂综合症蛋白1(Nijmegen breakage syndrome protein 1,Nbs1)和p38丝裂原活化蛋白激酶(p38mitogen activatedprotein kinase,p38MAPK)等不同,形成了不同的ATM蛋白激酶依赖性信号转导通路。最近研究发现,ATM蛋白激酶依赖性信号转导通路参与细胞周期多个检测点的调控,在DNA双链断裂(DNA double-strand break,DSB)损伤修复过程中发挥着至关重要的作用,暗示了ATM蛋白激酶或将成为恶性肿瘤放射治疗增敏新靶点。
Mutations in the ataxia-telangiectasia mutated gene（ATM gene） lead to the genetic disorder ataxia-telangiectasia（A-T）.The ATM protein kinase,which is the product of the ATM gene,is mainly distributed in the nucleus of proliferating cells.Here we clarify the ATM-dependent signaling pathways according to phosphorylating various targets that include checkpoint kinase 2（Chk2）,Nijmegen breakage syndrome protein 1（Nbs1） and p38 mitogen activated protein kinase（p38MAPK） at different stages of the cell cycle.Recent studies reveal that the ATM-dependent signaling pathways involve in regulating multiple cell cycle checkpoints and play vital roles in repairing DNA double-strand breaks（DSBs） in the cell cycle,suggesting that the ATM kinase perhaps is a new target for radiosensitization in the radiotherapy of malignant neoplasms.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2012年第4期433-437,共5页
Fudan University Journal of Medical Sciences
作者简介
Corresponding author:乔田奎,E-mail:qiaotk@yahoo.com.
