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Article
Subject Categories: Chromatin & Transcription | Differentiation & Death
The EMBO Journal (2006) 25, 1680–1689, doi:10.1038/sj.emboj.7601066
Published online 6 April 2006
Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression
Sandrine Tyteca, Marie Vandromme, Gaëlle Legube, Martine Chevillard-Briet and Didier Trouche
Laboratoire de Biologie Moléculaire Eucaryote (LBME), UMR 5099 CNRS/Université Paul Sabatier, Institut d'Exploration Fonctionnelle des Génomes (IEFG), Toulouse, France

To whom correspondence should be addressed
Didier Trouche, Université Paul Sabatier, CNRS-LBME, Bat IBCG, 118, Route de Narbonne, 31062 Toulouse Cedex 9, France. Tel.: +33 5 61 33 59 15; Fax: +33 5 61 33 58 86; E-mail: trouche@ibcg.biotoul.fr

Received 24 October 2005; Accepted 7 March 2006; Published online 6 April 2006.
Abstract
The histone acetyl transferase Tip60 (HTATIP) belongs to a multimolecular complex involved in the cellular response to DNA damage. Tip60 participates in cell cycle arrest following DNA damage by allowing p53 to activate p21CIP (p21) expression. We show here that Tip60 and the E1A-associated p400 protein (EP400), which belongs to the Tip60 complex, are also required for DNA damage-induced apoptosis. Tip60 favours the expression of some proapoptotic p53 target genes most likely through the stimulation of p53 DNA binding activity. In contrast, p400 represses p21 expression in unstressed cells, thereby allowing cell cycle progression and DNA damage-induced apoptosis. Tip60 and p400 have thus opposite effects on p21 expression in the absence of DNA damage. We further found that this antagonism relies on the inhibition of Tip60 function by p400, a property that is abolished following DNA damage. Therefore, taken together, our results indicate that Tip60 and p400 play distinct roles in DNA damage-induced apoptosis and underline the importance of the Tip60 complex and its regulation in the proper control of cell fate.
Keywords: apoptosis, cell cycle, DNA damage, E1A-associated p400, Tip60 complex
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