TAB182对电离辐射诱发细胞周期G2/M阻滞的调节作用

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 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.

Involvement of TAB182 in Cell Cycle G2/M Arrest Induced by Ionizing Radiation

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 -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.