CDK-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10)
CDK-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10)
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DOI：
10.1074/jbc.m506745200
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发表时间：
2006-06-02
影响因子：
4.8
通讯作者：
Lee, Sheng-Chung
中科院分区：
文献类型：
--
作者：
Chou, Han-Yi E.;Chou, Han Ting;Lee, Sheng-Chung
聚（ADP-核糖）聚合酶（PARP）家族的蛋白质发挥广泛的功能，几乎涵盖DNA代谢和功能的每个方面，最显著的是响应DNA损伤、转录和维持基因组稳定性。在这里，我们报告了一个新的PARP家族成员，PARP 10（FLJ 14464或假设的蛋白质LOC 84875）的鉴定和表征。PARP 10的过表达导致细胞活力的丧失，尽管短发夹RNA的下调表达导致G（1）进展延迟和伴随的细胞死亡。PARP 10存在于细胞质和细胞核中，但只有核仁PARP 10在核仁组织区通过G1晚期到S期以及从前中期到胞质分裂获得依赖于CDK的磷酸化。PARP 10的PARP活性依赖于体外CDK 2-cyclin E的磷酸化。CDK磷酸化的PARP 10在生长停滞的细胞中不存在。这些结果表明，PARP 10在细胞增殖中起作用，并可作为增殖细胞的标志物。
Proteins of the poly(ADP-ribose) polymerase ( PARP) family play a wide array of functions, covering virtually every aspect of DNA metabolism and function, most notably with the response to DNA damage, transcription, and the maintenance of genomic stability. Here we report the identification and characterization of a novel PARP family member, PARP10 (FLJ14464 or hypothetical protein LOC84875). Overexpression of PARP10 results in loss of cell viability, although down-expression by short hairpin RNA leads to delayed G(1) progression and concomitant cell death. PARP10 exists in both cytoplasm and nucleus, but only nucleolar PARP10 acquires CDK-dependent phosphorylation through late-G1 to S phase, and from prometaphase to cytokinesis in the nucleolar organizing regions. The PARP activity of PARP10 depends on phosphorylation by CDK2-cyclin E in vitro. CDK-phosphorylated PARP10 is absent in growth-arrested cells. These results suggest that PARP10 functions in cell proliferation and may serve as a marker for proliferating cells.