title: Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis.
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.
authors.affiliation: Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Orazi
authors.forename: Barbara
authors.initials: B
authors.lastname: Cecchinelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bruno
authors.forename: Isabella
authors.initials: I
authors.lastname: Manni
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Saito
authors.forename: Monica
authors.initials: M
authors.lastname: Gostissa
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marchetti
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
authors.forename: Guilia
authors.initials: G
authors.lastname: Piaggio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.forename: Silvia
authors.initials: S
authors.lastname: Soddu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D004789:Enzyme Activation / Q000528:radiation effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D010766:Phosphorylation; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D012694:Serine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays
chemical_list: D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D012694:Serine; C115114:HIPK2 protein, human; C492003:Hipk2 protein, mouse; D017346:Protein Serine-Threonine Kinases