Mechanism of DNA-binding enhancement by the human T-cell leukaemia virus transactivator Tax

Abstract

Tax protein activates transcription of the human T-cell leukaemia virus type I (HTLV-I) genome through three imperfect cyclic AMP-responsive element (CRE) target sites located within the viral promoter. Previous work has shown that Tax interacts with the bZIP element of proteins that bind the CRE target site to promote peptide dimerization, suggesting an association between Tax and bZIP coiled coil. Here we show that the site of interaction with Tax is not the coiled coil, but the basic segment. This interaction increases the stability of the GCN4 bZIP dimer by 1.7 kcal mol-1 and the DNA affinity of the dimer by 1.9 kcal mol-1. The differential effect of Tax on several bZip-DNA complexes that differ in peptide sequence or DNA conformation suggests a model for Tax action based on stabilization of a distinct DNA-bound protein structure. This model may explain how Tax interacts with transcription factors of considerable sequence diversity to alter patterns of gene expression.

HIV-1 Tat Inhibits IL-2 Gene Transcription Through Qualitative and Quantitative Alterations of the Cooperative Rel/AP1 Complex Bound to the CD28RE/AP1 Composite Element of the IL-2 Promoter

“…The existence of a direct interaction between a transactivator viral protein and AP1 has already been proposed for the Tat protein of the Visna virus (60) and for the human T cell leukemia virus transactivator tax (61,62). Our results show that the effects of HIV-Tat on AP1 seem specific of composite elements as transactivation controlled by consensus AP1 sites was not affected by endogenous expression of Tat in the cell.…”

Mitochondrial factors with dual roles in death and survival

“…For example, if they act like a mitochondrial uncoupling protein by causing a proton leak across the inner mitochondrial membrane, they could potentially protect any type of cell from cell death by building up the respiratory function of cells in the event of an insult. In a similar manner, UCP2 was shown to inhibit cell death in neurons (Baranger et al, 1995). Thus, human Bcl-2 family proteins could theoretically act independently of all other yeast and plant proteins to explain their nearly universal ability to inhibit cell death.…”

Identification of the core domain and the secondary structure of the transcriptional coactivator MBF1

“…The Bombyx mori MBF1 binds to a DNA binding region of FTZ-F1, called FTZ-F1 box, and its yeast counterpart binds to the DNA binding basic region of the bZIP domain of GCN4 (Ueda et al 1992;Li et al 1994;Takemaru et al 1997;Takemaru et al 1998). The binding of MBF1 to FTZ-F1 or GCN4 stimulates their bindings to the target DNA sequences in a similar manner as the human T-cell leukaemia virus transactivator Tax does (Baranger et al 1995;Perini et al 1995). In this study, we identified the well-structured core domain of MBF1 which is capable of binding to TBP, and determined its secondary structure by NMR.…”