Human TAF _II 28 interacts with the human T cell leukemia virus type I Tax transactivator and promotes its transcriptional activity

Abstract

The Tax protein encoded by human T cell leukemia virus type I transactivates the viral promoter by forming a complex with several cellular factors bound to three repeats of a specific upstream regulatory sequence. We have shown that transactivation by Tax was correlated with its ability to interact with the C-terminal moiety of the TATA box-binding protein (TBP). In the present study, the ability of The viral protein Tax strongly activates transcription of the human T cell leukemia virus type I (HTLV-I) provirus and of a specific group of cellular genes (1). Various studies have established that Tax is recruited to the Tax-responsive element 1 of the HTLV-I promoter and to the serum-responsive element of the c-fos promoter (2-5) via interactions with cellular transcription factors. In agreement with this notion, a GAL4 DNA binding domain-Tax fusion protein stimulates transcription of a reporter gene under the control of GAL4 sites (6). Using this approach, we have shown that the transcriptional activity of the GAL4-Tax fusion protein involves a direct protein-protein interaction between Tax and TATA box-binding protein (TBP) (7).However, in vitro transcription experiments have established that activation by Tax requires the transcription factor complex TFIID comprised of TBP and TBP-associated factors (TAF II s) (8). To better understand the molecular mechanisms underlying activation by Tax, we investigated the interactions between Tax and hTAF II s. These experiments show a selective interaction of Tax with hTAF II 28. Increasing the intracellular concentration of hTAF II 28 augments the activity of GAL4-Tax, and the overexpression of both TBP and hTAF II 28 resulted in an additive increase in activation. The ability of hTAF II 28 to potentiate activation by Tax was dependent on its ability to interact with TBP. These observations support the notion that Tax activates transcription by interacting with TFIID through both TBP and hTAF II 28. MATERIALS AND METHODSTransfections. HeLa cells and COS-7 cells, grown in monolayers to 40% (HeLa cells) or 80% (COS-7 cells) confluence, were transfected by the calcium phosphate coprecipitation method (7). The total amount of simian virus 40 promotercontaining plasmids was adjusted to a constant level with pSG5, and the total amount of cytomegalovirus promotercontaining plasmids was adjusted to a constant level with pXJ41.

Synergistic Transcriptional Activation by TATA-Binding Protein and hTAFII28 Requires Specific Amino Acids of the hTAFII28 Histone Fold

“…Coexpression of hTAF II 28 and/or TBP strongly potentiates activation by the viral Tax protein, and Tax interacts directly with hTAF II 28 and TBP to form a ternary complex (8).…”

The Human Transcription Factor IID Subunit Human TATA-binding Protein-associated Factor 28 Interacts in a Ligand-reversible Manner with the Vitamin D3 and Thyroid Hormone Receptors

“…Expression of hTAF II 28 also potentiates activation by the ligand-dependent activation function-2 of the nuclear receptors (NRs) for vitamin D 3 (VDR), 9-cis retinoic acid (RXR), and estrogen (29,30). Coexpression of TBP and hTAF II 28 shows that they act synergistically to potentiate activation by the VDR or estrogen receptor.…”

“…Expression of hTAF II 28 also potentiates activation by the ligand-dependent activation function-2 of the nuclear receptors (NRs) for vitamin D 3 (VDR), 9-cis retinoic acid (RXR), and estrogen (29,30). Coexpression of TBP and hTAF II 28 shows that they act synergistically to potentiate activation by the VDR or estrogen receptor. This synergism requires specific amino acids of the hTAF II 28 histone fold domain located in the conserved C-terminal half of the protein and can also be abolished by a mutation in the H1Ј helix of TBP (31,32).…”

“…An increasing body of results also shows that human TAF II 28 (hTAF II 28), hTAF II 135, and hTAF II 105 can act as specific transcriptional coactivators in mammalian cells. For example, distinct domains of hTAF II 135 interact specifically with Sp1, cAMP response element-binding protein, and E1A, and coexpression of these hTAF II 135 derivatives has a dominant negative effect on the activity of these activators (22)(23)(24)(25), whereas coexpression of hTAF II 135 strongly potentiates transcriptional activation by several nuclear receptors (26).…”

“…The viral protein Tax interacts directly with hTAF II 28, and coexpression of hTAF II 28 strongly potentiates activation by Tax (28). Expression of hTAF II 28 also potentiates activation by the ligand-dependent activation function-2 of the nuclear receptors (NRs) for vitamin D 3 (VDR), 9-cis retinoic acid (RXR), and estrogen (29,30).…”