CK2 inhibits apoptosis and changes its cellular localization following ionizing radiation.
CK2 inhibits apoptosis and changes its cellular localization following ionizing radiation.
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DOI：
10.1158/0008-5472.can-04-3941
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发表时间：
2005-05
期刊：
影响因子：
11.2
通讯作者：
K. Yamane;T. Kinsella
中科院分区：
文献类型：
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作者：
K. Yamane;T. Kinsella
在这项研究中，我们证明 CK2（酪蛋白激酶 II，CKII）参与电离辐射 (IR) 后的细胞凋亡反应。使用 HeLa 人宫颈癌细胞，我们发现，与对照小干扰 RNA 相比，通过流式细胞术技术测量，转染针对 CK2 α 和/或 α' 催化亚基的小干扰 RNA 会导致 IR 损伤后细胞凋亡增强。在 IR 2 至 6 小时内，CK2 α 部分定位于核周结构，而 α' 发生明显的核定位。用泛半胱天冬酶抑制剂治疗或转染 ARC（具有半胱天冬酶募集结构域的细胞凋亡阻遏蛋白）可抑制 CK2 减少的细胞中对 IR 的凋亡反应，表明半胱天冬酶的参与。此外，我们发现 CK2 α 和/或 α' 的减少会影响该人类细胞系中的细胞周期进程，与 IR 损伤无关。然而，IR后的G2-M检查点在CK2α和/或α'减少的细胞中不受影响。因此，我们的数据表明 CK2 参与细胞凋亡的抑制，并在 IR 损伤后负向调节 caspase 活性。
In this study, we show that CK2 (casein kinase II, CKII) participates in apoptotic responses following ionizing radiation (IR). Using HeLa human cervical carcinoma cells, we find that transfection of small interfering RNA against the CK2 alpha and/or alpha' catalytic subunits results in enhanced apoptosis following IR damage as measured by flow cytometry techniques, compared with a control small interfering RNA. Within 2 to 6 hours of IR, CK2 alpha partially localizes to perinuclear structures, whereas a marked nuclear localization of alpha' occurs. Treatment with a pan-caspase inhibitor or transfection of ARC (apoptosis repressor with caspase recruitment domain) suppresses the apoptotic response to IR in the CK2-reduced cells, indicating involvement of caspases. Additionally, we find that CK2 alpha and/or alpha' reduction affects cell cycle progression independent of IR damage in this human cell line. However, the G2-M checkpoint following IR is not affected in CK2 alpha- and/or alpha'-reduced cells. Thus, our data suggest that CK2 participates in inhibition of apoptosis and negatively regulates caspase activity following IR damage.