Human T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein/p300

The highly conserved coadapters CREB binding protein (CBP) and p300 form co mplexes with CREB as well as other DNA binding transcription factors to mod ulate chromatin remodeling and thus transcription. Human T-lymphotropic vir us type 1 (HTLV-1) transcription is controlled, in part, by the CREB/ATF fa mily of transcription factors which bind promoter sequences and function as complexes with the viral oncogenic protein Tax. We have reported that the nuclear localizing protein p30(II) of HTLV-1 functions as a transcription f actor, differentially modulates CREB-responsive promoters, and is critical for maintenance of proviral loads in rabbits. In this study, we tested whet her p30(II) directly interacts with CBP/p300 to modulate gene transcription . Gal4(BD)-p30(II)-mediated transactivation was enhanced following exogenou s expression of p300 and was competitively repressed by the p300 binding pr otein, adenovirus E1A, and E1ACR2 (mutated for retinoblastoma binding but r etaining p300 binding). In contrast, E1ACR1 (mutated for p300 binding) fail ed to alter Gal4(BD)-p30(II)-mediated transactivation. In addition, Gal4(BD )-p30(II)-mediated transactivation was competitively inhibited by the cotra nsfection of CMV-p30(II)-HA and CMV-Tax but could be rescued by exogenous p 300. Importantly, we demonstrate that p30(II) colocalizes with p300 in cell nuclei and directly binds to CBP/p300 in cells. Deletion mutants of CBP/p3 00 were used to localize the site critical for binding p30(II) to a highly conserved KIX region. DNA binding assays confirmed the interference of p30( II) with the assembly of CREB-Tax-p300/CBP multiprotein complexes on 21-bp repeat oligonucleotides in vitro. Collectively, our results demonstrate tha t CBP/p300 is a cellular protein target for HTLV-1 p30(II) and mediates its transcriptional effects in vivo.