DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes
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...
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| Veröffentlicht in: | Molecular cell 2002, Vol.9 (1), p.175-186 |
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| creator | Costanzo, Antonio Merlo, Paola Pediconi, Natalia Fulco, Marcella Sartorelli, Vittorio Cole, Philip A. Fontemaggi, Giulia Fanciulli, Maurizio Schiltz, Louis Blandino, Giovanni Balsano, Clara Levrero, Massimo |
| description | 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. |
| doi_str_mv | 10.1016/S1097-2765(02)00431-8 |
| format | Article |
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−/− 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.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/S1097-2765(02)00431-8</identifier><identifier>PMID: 11804596</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acetylation ; Apoptosis - genetics ; Apoptosis Regulatory Proteins ; c-Abl protein ; 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 ; p53AIP1 gene ; p73 protein ; Proteins - genetics ; Proteins - metabolism ; Tumor Cells, Cultured ; Tumor Protein p73 ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins</subject><ispartof>Molecular cell, 2002, Vol.9 (1), p.175-186</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-66e26d254d366d49d589b6b75bbf1403eaa57d4dd42556d289627d520597ce2c3</citedby><cites>FETCH-LOGICAL-c493t-66e26d254d366d49d589b6b75bbf1403eaa57d4dd42556d289627d520597ce2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276502004318$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11804596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costanzo, Antonio</creatorcontrib><creatorcontrib>Merlo, Paola</creatorcontrib><creatorcontrib>Pediconi, Natalia</creatorcontrib><creatorcontrib>Fulco, Marcella</creatorcontrib><creatorcontrib>Sartorelli, Vittorio</creatorcontrib><creatorcontrib>Cole, Philip A.</creatorcontrib><creatorcontrib>Fontemaggi, Giulia</creatorcontrib><creatorcontrib>Fanciulli, Maurizio</creatorcontrib><creatorcontrib>Schiltz, Louis</creatorcontrib><creatorcontrib>Blandino, Giovanni</creatorcontrib><creatorcontrib>Balsano, Clara</creatorcontrib><creatorcontrib>Levrero, Massimo</creatorcontrib><title>DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>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.</description><subject>Acetylation</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis Regulatory Proteins</subject><subject>c-Abl protein</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - genetics</subject><subject>Cyclins - metabolism</subject><subject>DNA Damage</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>p53AIP1 gene</subject><subject>p73 protein</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Protein p73</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctKxDAUhoMoXkYfQclKdFFN0iRtV1Km3mDQhboOaXKqkU5bm8yAb2_mgi5dncPhO7f_R-iUkitKqLx-oaTIEpZJcUHYJSE8pUm-gw7XZU4l393mK-QAHXn_SQjlIi_20QGlOeGikIfIVE8lrvRcv0NSwQCdhS7g0kD4bnVwfYf7Bg9Ziitngg7gcfgA_AItmOCWEMkYfsFy6IfQB2fwqx7fIeB76MAfo71Gtx5OtnGC3u5uX6cPyez5_nFazhLDizQkUgKTlgluUyktL2y8tZZ1Juq6oZykoLXILLeWMyEimBeSZVYwIorMADPpBJ1v5g5j_7UAH9TceQNtqzvoF15l8X2Rp-xfkOYsT-MRERQb0Iy99yM0ahjdXI_fihK1skGtbVArjRVham2DymPf2XbBop6D_eva6h6Bmw0AUY-lg1F546AzYN0YlVW2d_-s-AGrIZXo</recordid><startdate>2002</startdate><enddate>2002</enddate><creator>Costanzo, Antonio</creator><creator>Merlo, Paola</creator><creator>Pediconi, Natalia</creator><creator>Fulco, Marcella</creator><creator>Sartorelli, Vittorio</creator><creator>Cole, Philip A.</creator><creator>Fontemaggi, Giulia</creator><creator>Fanciulli, Maurizio</creator><creator>Schiltz, Louis</creator><creator>Blandino, Giovanni</creator><creator>Balsano, Clara</creator><creator>Levrero, Massimo</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>2002</creationdate><title>DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes</title><author>Costanzo, Antonio ; Merlo, Paola ; Pediconi, Natalia ; Fulco, Marcella ; Sartorelli, Vittorio ; Cole, Philip A. ; Fontemaggi, Giulia ; Fanciulli, Maurizio ; Schiltz, Louis ; Blandino, Giovanni ; Balsano, Clara ; Levrero, Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-66e26d254d366d49d589b6b75bbf1403eaa57d4dd42556d289627d520597ce2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Acetylation</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis Regulatory Proteins</topic><topic>c-Abl protein</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - genetics</topic><topic>Cyclins - metabolism</topic><topic>DNA Damage</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>p53AIP1 gene</topic><topic>p73 protein</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Protein p73</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Costanzo, Antonio</creatorcontrib><creatorcontrib>Merlo, Paola</creatorcontrib><creatorcontrib>Pediconi, Natalia</creatorcontrib><creatorcontrib>Fulco, Marcella</creatorcontrib><creatorcontrib>Sartorelli, Vittorio</creatorcontrib><creatorcontrib>Cole, Philip A.</creatorcontrib><creatorcontrib>Fontemaggi, Giulia</creatorcontrib><creatorcontrib>Fanciulli, Maurizio</creatorcontrib><creatorcontrib>Schiltz, Louis</creatorcontrib><creatorcontrib>Blandino, Giovanni</creatorcontrib><creatorcontrib>Balsano, Clara</creatorcontrib><creatorcontrib>Levrero, Massimo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costanzo, Antonio</au><au>Merlo, Paola</au><au>Pediconi, Natalia</au><au>Fulco, Marcella</au><au>Sartorelli, Vittorio</au><au>Cole, Philip A.</au><au>Fontemaggi, Giulia</au><au>Fanciulli, Maurizio</au><au>Schiltz, Louis</au><au>Blandino, Giovanni</au><au>Balsano, Clara</au><au>Levrero, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2002</date><risdate>2002</risdate><volume>9</volume><issue>1</issue><spage>175</spage><epage>186</epage><pages>175-186</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11804596</pmid><doi>10.1016/S1097-2765(02)00431-8</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylation Apoptosis - genetics Apoptosis Regulatory Proteins c-Abl protein 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 p53AIP1 gene p73 protein Proteins - genetics Proteins - metabolism Tumor Cells, Cultured Tumor Protein p73 Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins |
| title | DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes |
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