title: Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53.
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.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kai-Wei
authors.initials: KW
authors.lastname: Hsueh
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Fu
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.forename: Chao-Hsiung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D064127:Aurora Kinases; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012261:Ribonucleoproteins; D016159:Tumor Suppressor Protein p53; C072074:HNRNPK protein, human; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases