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  • Original Paper
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Utilization of the CBP but not the p300 co-activator by human T-lymphotropic virus type-2 Tax for p53 inhibition

Oncogene volume 23, pages 5447–5458 (2004)Cite this article

Abstract

We previously reported, both in transfected cells and in human T-cell leukemia virus type-2 subtype B infected cells, that the viral transactivator Tax-2B protein could inhibit p53 functions. We have now investigated the mechanism through which Tax-2B represses p53 using GFPTax-2B fusion proteins. We present evidence that Tax-2B inhibition of p53 function is not linked to CREB/ATF activation, but is uniquely correlated with the interaction of CREB binding protein (CBP), but not p300, with the C-terminus of Tax-2B. Wild type, but not a Tax-2B-M47 mutant, inhibits p53 function in adherent cells. We demonstrate that both Tax-2B and Tax-2B-M47 can bind p300, while Tax-2B-M47 is impaired for CBP binding. Importantly, transfection of increasing amounts of CBP but not p300 or p300/CBP-associated factor (P/CAF) could rescue p53 transcriptional activity in the presence of Tax-2B in nonlymphocytic cells. In lymphoid cells, Tax-2B mediated inhibition of p53 is correlated with the NF-κB pathway activation and could be prevented by the overexpression of an IκBα mutant. Given the similarities between the functional domains of CBP and p300, these results are intriguing and suggest that Tax-2B must bind the CR2 domain of CBP, but not that of p300 in order to repress p53.

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Acknowledgements

We are indebted to Drs WC Greene, Y Nakatani, C Salaün, N Sol-Foulon, K Schwamborn, P Green, WW Hall and PG Pelicci for the generous gifts of reagents essential to the realization of this study.

This work was supported by grants from l'Association de Recherche sur le Cancer (ARC #4781) from ARECA and from la Fondation de France to RM and fellowships from le Ministère de la Recherche, CANAM and Pasteur Weizmann to LM. RM is supported by INSERM.

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Authors and Affiliations

  1. Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris cedex, France

    Laurent Meertens, Nelly Quere, Antoine Gessain & Renaud Mahieux

  2. Virus Tumor Biology Section, NCI, NIH, Bethesda, MA, USA

    Cynthia Pise-Masison & John Brady

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  1. Laurent Meertens
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Correspondence to Renaud Mahieux.

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Meertens, L., Pise-Masison, C., Quere, N. et al. Utilization of the CBP but not the p300 co-activator by human T-lymphotropic virus type-2 Tax for p53 inhibition. Oncogene 23, 5447–5458 (2004). https://doi.org/10.1038/sj.onc.1207719

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