DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes

Antonio Costanzo; Paola Merlo; Natalia Pediconi; Marcella Fulco; Vittorio Sartorelli; Philip A. Cole; Giulia Fontemaggi; Maurizio Fanciulli; Louis Schiltz; Giovanni Blandino; Clara Balsano; Massimo Levrero

doi:10.1016/S1097-2765(02)00431-8

DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes

Antonio Costanzo, Paola Merlo, Natalia Pediconi, Marcella Fulco, Vittorio Sartorelli, Philip A. Cole, Giulia Fontemaggi, Maurizio Fanciulli, Louis Schiltz, Giovanni Blandino, Clara Balsano, Massimo Levrero

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273 Scopus citations

Abstract

The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53^-/- background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes.

Original language	English (US)
Pages (from-to)	175-186
Number of pages	12
Journal	Molecular cell
Volume	9
Issue number	1
DOIs	https://doi.org/10.1016/S1097-2765(02)00431-8
State	Published - 2002
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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title = "DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes",

abstract = "The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53-/- background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes.",

author = "Antonio Costanzo and Paola Merlo and Natalia Pediconi and Marcella Fulco and Vittorio Sartorelli and Cole, {Philip A.} and Giulia Fontemaggi and Maurizio Fanciulli and Louis Schiltz and Giovanni Blandino and Clara Balsano and Massimo Levrero",

note = "Funding Information: This work is dedicated to the memory of Franco Tat{\`o}, mentor, friend, and colleague. We thank P.L. Puri for critically reading the manuscript and helpful suggestions. This work was supported by grants from AIRC, MURST-Cofin, Telethon, ISS-Viral Hepatitis Project, and Schering-Plough to M.L. and by National Institutes of Health grants to P.A.C. P.M., N.P., and M.F. are supported by fellowships from the Fondazione A. Cesalpino.",

year = "2002",

doi = "10.1016/S1097-2765(02)00431-8",

language = "English (US)",

volume = "9",

pages = "175--186",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes

AU - Costanzo, Antonio

AU - Merlo, Paola

AU - Pediconi, Natalia

AU - Fulco, Marcella

AU - Sartorelli, Vittorio

AU - Cole, Philip A.

AU - Fontemaggi, Giulia

AU - Fanciulli, Maurizio

AU - Schiltz, Louis

AU - Blandino, Giovanni

AU - Balsano, Clara

AU - Levrero, Massimo

N1 - Funding Information: This work is dedicated to the memory of Franco Tatò, mentor, friend, and colleague. We thank P.L. Puri for critically reading the manuscript and helpful suggestions. This work was supported by grants from AIRC, MURST-Cofin, Telethon, ISS-Viral Hepatitis Project, and Schering-Plough to M.L. and by National Institutes of Health grants to P.A.C. P.M., N.P., and M.F. are supported by fellowships from the Fondazione A. Cesalpino.

PY - 2002

Y1 - 2002

N2 - The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53-/- background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes.

AB - The tumor suppressor p53 and its close relative p73 are activated in response to DNA damage resulting in either cell cycle arrest or apoptosis. Here, we show that DNA damage induces the acetylation of p73 by the acetyltransferase p300. Inhibiting the enzymatic activity of p300 hampers apoptosis in a p53-/- background. Furthermore, a nonacetylatable p73 is defective in activating transcription of the proapoptotic p53AIP1 gene but retains an intact ability to regulate other targets such as p21. Finally, p300-mediated acetylation of p73 requires the protooncogene c-abl. Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes.

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DO - 10.1016/S1097-2765(02)00431-8

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AN - SCOPUS:18244408596

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SP - 175

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JO - Molecular cell

JF - Molecular cell

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DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes

Abstract

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