极光激酶 A 使 hnRNPK 磷酸化并破坏其与 p53 的相互作用。

Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53.

机构信息

Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.

出版信息

FEBS Lett. 2011 Sep 2;585(17):2671-5. doi: 10.1016/j.febslet.2011.07.031. Epub 2011 Aug 3.

DOI:10.1016/j.febslet.2011.07.031

Abstract

Amplification of Aurora-A, encoding a cell cycle-regulating kinase, has been reported in human cancers. Although Aurora-A is known to directly phosphorylate and down-regulate p53, the detailed mechanism remains unclear. Here we show that Aurora-A phosphorylates hnRNPK, a transcriptional coactivator of p53, on serine 379. This phosphorylation does not affect the post-transcriptional activity or cellular localization of hnRNPK, but disrupts its interaction with p53. Inverse correlation between Aurora-A activity and hnRNPK-p53 interaction was further demonstrated in DNA-damaged cells. Our results provide an alternative mechanism, whereby via phosphorylating hnRNPK Aurora-A participates in regulating p53 activity during DNA damage.

摘要

极光激酶 A 的扩增，编码细胞周期调节激酶，已在人类癌症中报道。尽管已知极光激酶 A 可直接磷酸化并下调 p53，但详细机制尚不清楚。在这里，我们显示极光激酶 A 在丝氨酸 379 上磷酸化 hnRNPK，p53 的转录共激活因子。这种磷酸化不影响 hnRNPK 的转录后活性或细胞定位，但破坏其与 p53 的相互作用。在 DNA 损伤细胞中进一步证明了极光激酶 A 活性和 hnRNPK-p53 相互作用之间的负相关。我们的结果提供了一种替代机制，即通过磷酸化 hnRNPK，极光激酶 A 参与调节 DNA 损伤过程中的 p53 活性。