Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53

AbstractAmplification 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.Structured summary of protein interactionsAurora-Aphysically interactswithhnRNPK by anti tag coimmunoprecipitation(View interaction)p53physically interactswithhnRNPK by pull down(View interaction)p53physically interactswithhnRNPK by anti bait coimmunoprecipitation(View interaction)hnRNPKphysically interactswithp53 by anti bait coimmunoprecipitation(View interaction)Aurora-A phosphorylates hnRNPKby protein kinase assay(View interaction)hnRNPKphysically interactswithAurora-A by anti bait coimmunoprecipitation(View interaction