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  • Original Paper
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HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

Oncogene volume 19, pages 2155–2164 (2000)Cite this article

Abstract

The c-Myb proto-oncogene is preferentially expressed in hematopoietic lineages, and highly expressed in several leukemia types. The Human T-cell Leukemia Virus Type I (HTLV-I) is the etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL). A previous report suggested that Tax, the viral transactivator, is able to suppress the transactivation potential of c-Myb protein by competing for recruitment of CBP. We tested whether such a competition could affect transcription from the c-Myb promoter in Tax expressing T-cells. Using several c-Myb promoter reporter constructs carrying mutations in various regions, we demonstrate that Tax suppression of c-Myb transactivation results in transrepression of the c-Myb promoter through the Myb responsive elements in Jurkat T-cells. The ability of Tax mutants M22, M47 and V89A to interact with the full-length CBP and p300 proteins in vitro, and their ability to repress the c-Myb promoter, was then evaluated. Although both M47 and M22 bind to CBP and p300 to a similar extent, only M47 was able to repress the c-Myb promoter, suggesting that competition for CBP/p300 binding was not the mechanism underlying Tax's effect. This concept was further supported by the fact that the Tax mutant V89A transrepresses the c-Myb promoter efficiently in spite of an impaired binding to CBP and p300. Therefore, Tax-mediated repression of the c-Myb promoter appears to be independent from a direct competition between c-Myb and Tax for recruitment of CBP/p300. Interestingly, a decreased transcription from the endogenous c-Myb promoter was observed in several HTLV-I transformed T-cell lines. Finally, the ability of Tax to directly repress the endogenous c-Myb promoter was demonstrated in a Jurkat cell line stably transfected with a tax gene driven by a cadmium-inducible promoter.

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Acknowledgements

The authors would like to thank Dr RH Goodman (The Vollum Institute, Portland, OR, USA); Dr D Livingston (Harvard Medical School, Boston, MA, USA); Dr L Boxer (Stanford University School of Medicine, Stanford CA, USA); Dr CZ Giam (Uniformed Services University of the Health Sciences, Bethesda, MD, USA) for gifts of reagents and Steven Snodgrass for editorial assistance.

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Authors and Affiliations

  1. Division of Basic Sciences, Basic Research Laboratory, National Cancer Institute, Bethesda, 20814, Maryland, MD, USA

    Christophe Nicot, Anna Cereseto & Genoveffa Franchini

  2. Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, 20814, Maryland, MD, USA

    Renaud Mahieux & John N Brady

  3. Laboratory of Cellular Oncology, National Institutes of Health, Bethesda, 20892, Maryland, MD, USA

    Rene Opavsky & Linda Wolff

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  1. Christophe Nicot
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Nicot, C., Mahieux, R., Opavsky, R. et al. HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300. Oncogene 19, 2155–2164 (2000). https://doi.org/10.1038/sj.onc.1203536

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