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

Christophe Nicot, Renaud Mahieux, Rene Opavsky, Anna Cereseto, Linda Wolff, John N. Brady, Genoveffa Franchini

Research output: Contribution to journalArticle

34 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)2155-2164
Number of pages10
JournalOncogene
Volume19
Issue number17
DOIs
StatePublished - Apr 20 2000

Keywords

  • CBP/p300
  • Tax
  • Transrepression
  • c-Myb

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Nicot, C., Mahieux, R., Opavsky, R., Cereseto, A., Wolff, L., Brady, J. N., & Franchini, G. (2000). HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300. Oncogene, 19(17), 2155-2164. https://doi.org/10.1038/sj.onc.1203536