Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate
Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate
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DOI：
10.1073/pnas.1106136108
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发表时间：
2011-06-14
影响因子：
11.1
通讯作者：
Elledge, Stephen J.
中科院分区：
文献类型：
--
作者：
Emanuele, Michael J.;Ciccia, Alberto;Elledge, Stephen J.
后期促进复合物/环体（APC/C）是一种细胞周期调节的E3泛素连接酶，控制有丝分裂出口和整个G1期底物蛋白的降解。我们已经确定了APC/C底物和细胞周期调节蛋白，KIAA 0101/PAF 15。PAF 15蛋白水平在细胞周期的G2/M期达到峰值，并在有丝分裂退出时以APC/C和KEN盒依赖性方式迅速下降。PAF 15与增殖细胞核抗原（PCNA）相关，PAF 15的缺失减少了S期细胞的数量，提示其在细胞周期调节中的作用。照射后，PAF 15与γ H2 AX通过与PCNA的相互作用在DNA损伤部位共定位。最后，PAF 15耗竭导致同源重组介导的DNA修复增加，并且过度表达导致对UV诱导的DNA损伤的敏感性。我们的结论是，PAF 15是一个APC/C调节蛋白参与细胞周期进程和DNA损伤反应。
The anaphase-promoting complex/cyclosome (APC/C) is a cell cycle-regulated E3 ubiquitin ligase that controls the degradation of substrate proteins at mitotic exit and throughout the G1 phase. We have identified an APC/C substrate and cell cycle-regulated protein, KIAA0101/PAF15. PAF15 protein levels peak in the G2/M phase of the cell cycle and drop rapidly at mitotic exit in an APC/C- and KEN-box-dependent fashion. PAF15 associates with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation. Following irradiation, PAF15 colocalized with gamma H2AX foci at sites of DNA damage through its interaction with PCNA. Finally, PAF15 depletion led to an increase in homologous recombination-mediated DNA repair, and overexpression caused sensitivity to UV-induced DNA damage. We conclude that PAF15 is an APC/C-regulated protein involved in both cell cycle progression and the DNA damage response.