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.

DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes / Antonio, Costanzo; Paola, Merlo; Pediconi, Natalia; Marcella, Fulco; Vittorio, Sartorelli; Philip A., Cole; Giulia, Fontemaggi; Maurizio, Fanciulli; Louis, Schiltz; Giovanni, Blandino; Clara, Balsano; Levrero, Massimo. - In: MOLECULAR CELL. - ISSN 1097-2765. - 9:1(2002), pp. 175-186. [10.1016/s1097-2765(02)00431-8]

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

PEDICONI, NATALIA;LEVRERO, Massimo
2002

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.
2002
Cultured, Acetylation, Apoptosis Regulatory Proteins, Apoptosis; genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclins; genetics/metabolism, DNA Damage, DNA-Binding Proteins; genetics/metabolism, Gene Expression Regulation, Genes; Tumor Suppressor, Humans, Nuclear Proteins; genetics/metabolism, Proteins; genetics/metabolism, Tumor Suppressor Protein p53; genetics/metabolism, Tumor Suppressor Proteins
01 Pubblicazione su rivista::01a Articolo in rivista
DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes / Antonio, Costanzo; Paola, Merlo; Pediconi, Natalia; Marcella, Fulco; Vittorio, Sartorelli; Philip A., Cole; Giulia, Fontemaggi; Maurizio, Fanciulli; Louis, Schiltz; Giovanni, Blandino; Clara, Balsano; Levrero, Massimo. - In: MOLECULAR CELL. - ISSN 1097-2765. - 9:1(2002), pp. 175-186. [10.1016/s1097-2765(02)00431-8]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/438491
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