Human T-cell leukemia virus type I tax repression of p73beta is mediated through competition for the C/H1 domain of CBP.

The Tax protein, encoded by the human T-cell leukemia virus type I (HTLV-I), is required for high level viral transcription and HTLV-I-associated malignant transformation. Although the precise mechanism of malignant transformation by Tax is unclear, it is well established that Tax represses the transcription function of the tumor suppressor p53, possibly accelerating the accumulation of genetic mutations that are critical in HTLV-I-mediated malignant transformation. Tax repression of p53 transcription function appears to occur, at least in part, through competition for the cellular coactivator CBP/p300. In this study, we characterize the effect of Tax on the p53 family member, p73. We demonstrate that Tax also represses the transcription function of p73beta and that the repression is reciprocal in vivo, consistent with the idea that both transcription factors may compete for CBP/p300 in vivo. We provide evidence showing that both Tax and p73 interact strongly with the C/H1 domain of CBP and that their binding to this region is mutually exclusive in vitro. This finding provides evidence supporting the idea that reciprocal transcriptional repression between Tax and p73 is mediated through coactivator competition.