Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis

Gabriella D'Orazi, Barbara Cecchinelli, Tiziana Bruno, Isabella Manni, Yuichiro Higashimoto, Shin'ichi Saito, Monica Gostissa, Sabrina Coen, Alessandra Marchetti, Giannino Del Sal, Giulia Piaggio, Maurizio Fanciulli, Ettore Appella, Silvia Soddu

Research output: Contribution to journalArticle

Abstract

Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity. Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46. HIPK2 localizes with p53 and PML-3 into the nuclear bodies and is activated after irradiation with ultraviolet. Antisense inhibition of HIPK2 expression reduces the ultraviolet-induced apoptosis. Furthermore, HIPK2 and p53 cooperate in the activation of p53-dependent transcription and apoptotic pathways. These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis.

Original languageEnglish
Pages (from-to)11-20
Number of pages10
JournalNature Cell Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Cell Biology

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