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| Subject Categories: Proteins | Genome Stability & Dynamics |
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| The EMBO Journal
(2002) 21, 1704–1712, doi: 10.1093/emboj/21.7.1704 |
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| Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation |
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| Gaëlle Legube1, Laetitia K. Linares2, Claudie Lemercier3, Martin Scheffner2, Saadi Khochbin3 and Didier Trouche1 |
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1 Laboratoire de Biologie Moléculaire Eucaryote, CNRS UMR 5099, 118 Route de Narbonne, Université Paul Sabatier, 31062 Toulouse, France 2 Institut für Biochemie, Universität zu Köln, D-50931 Köln, Germany 3 INSERM U309, Institut Albert Bonniot, 38706 La Tronche Cedex, France To whom correspondence should be addressed Didier Trouche, trouche@ibcg.biotoul.fr Received 13 July 2001; Revised 11 February 2002; Accepted 18 February 2002. |
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| Abstract |
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Acetylation is a prominent post-translational modification of nucleosomal histone N-terminal tails, which regulates chromatin accessibility. Accordingly, histone acetyltransferases (HATs) play major roles in processes such as transcription. Here, we show that the HAT Tip60, which is involved in DNA repair and apoptosis following  irradiation, is subjected to proteasome-dependent proteolysis. Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation. Moreover, a ubiquitin ligase-defective mutant of Mdm2 had no effect on Tip60 stability. Our results indicate that Mdm2 targets both p53 and Tip60, suggesting that these two proteins could be co-regulated with respect to protein stability. Consistent with this hypothesis, Tip60 levels increased significantly upon UV irradiation of Jurkat cells. Collectively, our results suggest that degradation of Tip60 could be part of the mechanism leading to cell transformation by Mdm2. |
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| Keywords: histone acetyltransferase, Mdm2, proteasome, Tip60, ubiquitylation |
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