Article abstract
Nature Cell Biology 4, 11 - 19 (2001)
Published online: 3 December 2001 | doi:10.1038/ncb714
Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis
Gabriella D'Orazi1,3, Barbara Cecchinelli1, Tiziana Bruno2, Isabella Manni1, Yuichiro Higashimoto4, Shin'ichi Saito4, Monica Gostissa5, Sabrina Coen1, Alessandra Marchetti1, Giannino Del Sal5,6, Giulia Piaggio1, Maurizio Fanciulli2, Ettore Appella4 & Silvia Soddu1
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.
- Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy
- Cell Metabolism and Pharmacokinetics Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy
- Department of Oncology and Neurosciences, University 'G. D'Annunzio', Via dei Vestini 3, 66013 Chieti, Italy
- Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
- National Laboratory, Inter-University Consortium for Biotechnologies, AREA Science Park, Padriciano 99, 34012 Trieste, Italy
- Department of Biochemistry, Biophysics and Chemistry of Macromolecules, Via Giozgiezi 1, 34100 Trieste, Italy
Correspondence to: Silvia Soddu1 e-mail: soddu@ifo.it
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