Tax oncoprotein trans-represses endogenous B-myb promoter activity in human T cells

The B-myb gene was identified on the basis of its homology with the protoon cogene c-myb, homolog of the avian myeloblastosis virus (AMV) and avian leu kemia virus (E26) transforming genes. Several studies using antisense const ructs or antisense oligonucleotides as well as overexpression experiments s uggest that B-Myb plays an important role in the transition from G(1) to S phase of the cell cycle and that B-Myb expression is cell cycle regulated. We have previously demonstrated that the human T cell lymphotropic virus ty pe 1 (HTLV-1) trans-activator Tax is able to repress transcription from c-m yb promoter reporter constructs as well as from the endogenous c-myb promot er in human T cells and that this effect is mediated through inhibition of the cMyb trans-activating functions. Here we report that both HTLV-1 as wel l as HTLV-2 Tax proteins inhibit cMyb trans-activation in mouse embryo fibr oblasts (MEFs). In addition to c-Myb, B-Myb expression is also markedly dow nregulated in HTLV-1-transformed cells at both RNA and protein levels. Furt hermore, by using a Jurkat T cell line stably transfected with a tax gene d riven by a cadmium-inducible promoter (JPX9), we were able to demonstrate t hat Tax directly represses the endogenous B-myb promoter in T cells. Becaus e c-Myb and R-Myb have been involved in cell cycle progression, our results suggest that Tax, by repressing both c-Myb and B-Myb endogenous promoters, may bypass their requirement for cell cycle progression in HTLV-1-transfor med T cells.