中文摘要：

TAB182是一个端锚聚合酶1（tankyrase 1）结合蛋白,它在体外能够被tankyrase 1发生二磷酸腺苷核糖基化（PAR）修饰,其生物学功能目前尚不明确.本研究发现,TAB182蛋白水平受电离辐射诱导表达,HeLa细胞经过4 Gy照射处理时,TAB182在2 h表达含量最高;经过不同剂量照射处理,2 h后2 Gy、4 Gy照射剂量组HeLa细胞中TAB182的表达有明显增加.通过shRNA沉默HeLa细胞中TAB182基因表达,导致其对4 Gy及以下剂量γ辐射的敏感性增加,但对8 Gy大剂量照射的敏感性没有明显变化.与对照组相比,4 Gy照射诱发TAB182基因沉默细胞的G2/M期阻滞时间显著延长.抑制TAB182表达导致细胞中DNA损伤反应蛋白DNA-PKcs、ATM、Chk2的表达水平显著降低.实验结果提示,TAB182蛋白参与放射DNA损伤信号反应和调控细胞周期G2/M进程.

英文摘要：

TAB182 is a tankyrase 1-binding protein with the molecular weight of 182 kD.TAB182 can be ADP-ribosylated by tankyrase 1 in vitro.The biological function of TAB182 remains to be explored.In the present study we found that the expression of TAB182 was up-regulated by ionizing radiation.After 4 Gy irradiation,the expression of TAB182 in HeLa cells reached a peak at 2 hour point.When treated with different doses of radiation and harvested 2 hours later,the expression of TAB182 in HeLa cells was increased significantly in the 2 Gy and 4 Gy irradiation groups.ShRNA-mediated silencing of TAB182 significantly increased the sensitivity of HeLa cells to 4 Gy and lower doses γ-rays exposure but not to the doses of 8 Gy exposure.As compared to control,depletion of TAB182 led to a prolonged G2/M arrest after the cells were exposed to 4 Gy irradiation.Finally we found that depletion of TAB182 in HeLa cells resulted in decreased expression of DNA damage response proteins ATM,DNA-PKcs,Chk2.These results illustrated that TAB182 was involved in DNA damage response and regulation of cell cycle G2/M phase progression in response to radiation injury.