title: Activation of a Tip60/E2F1/ERCC1 network in human lung adenocarcinoma cells exposed to cisplatin.
abstract: The Tip60 and E2F1 proteins are key players of the cellular response induced by genotoxic stresses. Here, new insights into the involvement of both proteins during the DNA damage response are provided. We show that Tip60 interacts with E2F1 and promotes its acetylation. We identify the lysine residues 120/125 of the E2F1 protein as the prime target sites of Tip60 and show that acetylation at these sites promotes the accumulation of E2F1. Importantly, we demonstrate that cisplatin induces the accumulation of E2F1 in a Tip60-dependent manner. However, and in contrast to PCAF and p300, Tip60 is not required for the induction of apoptosis in cisplatin-treated cells. Instead, Tip60 and E2F1 are involved in the upregulation of the excision repair cross-complementation group 1 protein expression, an enzyme involved in the repair of cisplatin-induced DNA lesions. These findings identify Tip60 as a direct regulator of E2F1 and support their cooperative role in DNA repair.
authors.affiliation: Equipe Bases Moléculaires de la Progression des Cancers du Poumon, Centre de Recherche INSERM U823, Institut Albert Bonniot BP170, 38042 Grenoble Cedex 09, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Van Den Broeck
authors.forename: Damien
authors.initials: D
authors.lastname: Nissou
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.forename: Beatrice
authors.initials: B
authors.lastname: Eymin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gazzeri
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D050687:E2F1 Transcription Factor; D004720:Endonucleases; D051548:Histone Acetyltransferases; D008239:Lysine; D000074443:Lysine Acetyltransferase 5; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493753:E2F1 protein, human; C494360:EP300 protein, human; C098489:KAT5 protein, human; C071447:ERCC1 protein, human