Dynamic Regulation of the COP9 Signalosome in Response to DNA Damage
Dynamic Regulation of the COP9 Signalosome in Response to DNA Damage
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DOI：
10.1128/mcb.01598-13
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发表时间：
2014-03-01
影响因子：
5.3
通讯作者：
Sharon, Michal
中科院分区：
文献类型：
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作者：
Fuzesi-Levi, Maria G.;Ben-Nissan, Gili;Sharon, Michal
COP 9信号体（CSN）是一种进化上保守的蛋白质复合物，其通过控制cullin-RING-泛素连接酶的功能参与泛素/26 S蛋白酶体途径的调节。在破译其在各种细胞和发育过程中的关键作用方面取得了令人印象深刻的进展。然而，人们对协调其功能的基本监管原则知之甚少。通过生物化学和荧光显微镜分析，我们确定，该复合物是本地化的细胞质，核质，和染色质结合的馏分，每个不同的组成postertifictionally修饰的亚基，这取决于其在细胞内的位置。在细胞周期中，亚细胞定位之间的分离保持稳定。然而，在UV损伤后，观察到CSN复合物向细胞核中的剂量依赖性时间穿梭，伴随着CSN 1、CSN 3和CSN 8内特异性磷酸化的上调。总之，我们的研究结果表明，特定的时空组成的CSN是高度控制，使复杂的快速适应和响应DNA损伤。
The COP9 signalosome (CSN) is an evolutionarily conserved protein complex that participates in the regulation of the ubiquitin/26S proteasome pathway by controlling the function of cullin-RING-ubiquitin ligases. Impressive progress has been made in deciphering its critical role in diverse cellular and developmental processes. However, little is known about the underlying regulatory principles that coordinate its function. Through biochemical and fluorescence microscopy analyses, we determined that the complex is localized in the cytoplasm, nucleoplasm, and chromatin-bound fractions, each differing in the composition of posttranslationally modified subunits, depending on its location within the cell. During the cell cycle, the segregation between subcellular localizations remains steady. However, upon UV damage, a dose-dependent temporal shuttling of the CSN complex into the nucleus was seen, accompanied by upregulation of specific phosphorylations within CSN1, CSN3, and CSN8. Taken together, our results suggest that the specific spatiotemporal composition of the CSN is highly controlled, enabling the complex to rapidly adapt and respond to DNA damage.