Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53

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.Structured summary of protein interactionsAurora-A physically interacts with hnRNPK by anti tag coimmunoprecipitation (View interaction)p53 physically interacts with hnRNPK by pull down (View interaction)p53 physically interacts with hnRNPK by anti bait coimmunoprecipitation (View interaction)hnRNPK physically interacts with p53 by anti bait coimmunoprecipitation (View interaction)Aurora-AphosphorylateshnRNPK by protein kinase assay (View interaction)hnRNPK physically interacts with Aurora-A by anti bait coimmunoprecipitation (View interaction)

► We demonstrate that Aurora-A phosphorylates hnRNPK in vitro and in vivo.
► Aurora-A-induced S379 phosphorylation disrupts hnRNPK interaction with p53.
► p53-hnRNPK interaction is enhanced during DNA damage that inhibits Aurora-A activity.