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

Mol Cell. 2002 Jan;9(1):175-86. doi: 10.1016/s1097-2765(02)00431-8.

Authors

Antonio Costanzo¹, Paola Merlo, Natalia Pediconi, Marcella Fulco, Vittorio Sartorelli, Philip A Cole, Giulia Fontemaggi, Maurizio Fanciulli, Louis Schiltz, Giovanni Blandino, Clara Balsano, Massimo Levrero

Affiliation

¹ Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome La Sapienza, 00161, Rome, Italy.

PMID: 11804596
DOI: 10.1016/s1097-2765(02)00431-8

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Acetylation
Apoptosis / genetics*
Apoptosis Regulatory Proteins
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics
Cyclins / metabolism
DNA Damage*
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Gene Expression Regulation
Genes, Tumor Suppressor
Humans
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Proteins / genetics
Proteins / metabolism
Tumor Cells, Cultured
Tumor Protein p73
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism
Tumor Suppressor Proteins

Substances

Apoptosis Regulatory Proteins
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
DNA-Binding Proteins
Nuclear Proteins
P53AIP1 protein, human
Proteins
TP73 protein, human
Tumor Protein p73
Tumor Suppressor Protein p53
Tumor Suppressor Proteins