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

Fingerprint

Homeodomain Proteins
Protein Kinases
Apoptosis
Protein-Serine-Threonine Kinases
Nuclear Family
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. / D'Orazi, Gabriella; Cecchinelli, Barbara; Bruno, Tiziana; Manni, Isabella; Higashimoto, Yuichiro; Saito, Shin'ichi; Gostissa, Monica; Coen, Sabrina; Marchetti, Alessandra; Del Sal, Giannino; Piaggio, Giulia; Fanciulli, Maurizio; Appella, Ettore; Soddu, Silvia.

In: Nature Cell Biology, Vol. 4, No. 1, 2002, p. 11-20.

Research output: Contribution to journalArticle

D'Orazi, G, Cecchinelli, B, Bruno, T, Manni, I, Higashimoto, Y, Saito, S, Gostissa, M, Coen, S, Marchetti, A, Del Sal, G, Piaggio, G, Fanciulli, M, Appella, E & Soddu, S 2002, 'Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis', Nature Cell Biology, vol. 4, no. 1, pp. 11-20. https://doi.org/10.1038/ncb714
D'Orazi, Gabriella ; Cecchinelli, Barbara ; Bruno, Tiziana ; Manni, Isabella ; Higashimoto, Yuichiro ; Saito, Shin'ichi ; Gostissa, Monica ; Coen, Sabrina ; Marchetti, Alessandra ; Del Sal, Giannino ; Piaggio, Giulia ; Fanciulli, Maurizio ; Appella, Ettore ; Soddu, Silvia. / Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. In: Nature Cell Biology. 2002 ; Vol. 4, No. 1. pp. 11-20.
@article{8840f9a65ff3432987852d44862eac26,
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.",
author = "Gabriella D'Orazi and Barbara Cecchinelli and Tiziana Bruno and Isabella Manni and Yuichiro Higashimoto and Shin'ichi Saito and Monica Gostissa and Sabrina Coen and Alessandra Marchetti and {Del Sal}, Giannino and Giulia Piaggio and Maurizio Fanciulli and Ettore Appella and Silvia Soddu",
year = "2002",
doi = "10.1038/ncb714",
language = "English",
volume = "4",
pages = "11--20",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis

AU - D'Orazi, Gabriella

AU - Cecchinelli, Barbara

AU - Bruno, Tiziana

AU - Manni, Isabella

AU - Higashimoto, Yuichiro

AU - Saito, Shin'ichi

AU - Gostissa, Monica

AU - Coen, Sabrina

AU - Marchetti, Alessandra

AU - Del Sal, Giannino

AU - Piaggio, Giulia

AU - Fanciulli, Maurizio

AU - Appella, Ettore

AU - Soddu, Silvia

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=18244379872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244379872&partnerID=8YFLogxK

U2 - 10.1038/ncb714

DO - 10.1038/ncb714

M3 - Article

C2 - 11780126

AN - SCOPUS:18244379872

VL - 4

SP - 11

EP - 20

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 1

ER -