Abstract
Transforming viral proteins such as E1A force cells through the restriction point of the cell cycle into S phase by forming complexes with two cellular proteins1,2,3: the retinoblastoma protein (Rb)4, a transcriptional co-repressor5, and CBP/p300 (ref. 6), a transcriptional co-activator7,8,9. These two proteins locally influence chromatin structure: Rb recruits a histone deacetylase10,11,12, whereas CBP is a histone acetyltransferase13,14. Progression through the restriction point is triggered by phosphorylation of Rb, leading to disruption of Rb-associated repressive complexes and allowing the activation of S-phase genes15. Here we show that CBP, like Rb, is controlled by phosphorylation at the G1/S boundary, increasing its histone acetyltransferase activity. This enzymatic activation is mimicked by E1A.
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Acknowledgements
We thank Z. Mishal and A. Vervisch for help with cell-cycle analysis; T. Kouzarides, L. Meijer and D. A. Lawrence for the gift of materials; F. Dautry for critical reading of the manuscript; and A. Damany for her support. This work was supported by grants from the Ligue Nationale contre le Cancer, the Comité des Yvelines, the Comité de l'Essone and the Comité du Val de Marne, from the Association pour la Recherche sur le Cancer and from the Groupement des Entreprises Françaises dans la Lutte contre le Cancer. S.A.-S.-A. was awarded a fellowship from the Comité de la Haute-Saône; S.R., a travel award from the Colombian Government (Colciencias); F.-X.B., a fellowship from the Agence Nationale pour la Recherche sur le Sida; L.M.-J. and F.D., fellowships from the Comité de l'Essone.
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Ait-Si-Ali, S., Ramirez, S., Barre, FX. et al. Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A. Nature 396, 184–186 (1998). https://doi.org/10.1038/24190
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DOI: https://doi.org/10.1038/24190
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