Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins.

Abstract

Activation of the HTLV‐I promoter by the viral Tax1 transactivator is mediated by a 21 bp sequence motif imperfectly repeated three times and composed of three exactly conserved domains (A, B and C from 5′ to 3′). We show here that the Tax1 response requires the integrity of the B domain and of at least one of the flanking A or C domains. We have identified three cellular proteins which bind specifically to the 21 bp motif. One of these is the already well‐characterized transcription factor ATF. The other two, namely HEB1 and HEB2, are specific for the 21 bp motif. HEB1 can bind to either domain A or C, but binding of ATF and HEB2 is determined by domain B. However, neither domain B alone, nor ATF/CREB binding sites respond significantly to Tax1. We therefore propose that Tax1 induction of the 21 bp enhancer element requires interaction with the two different cellular proteins identified in this study: HEB1 and HEB2, rather than binding of the ATF factor.

Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation

“…Preparation on nuclear extracts and electrophoretic mobility shift assays Preparation of nuclear extract from either proliferating or NGF-di erentiated PC12 cells was carried out as previously described (Montagne et al, 1990). Complementary oligonucleotides corresponding to bases 771 through 786 in the wild-type p21 promoter and the mutant promoter constructs Mut 2.2 and Mut 2.3 were synthetised, annealed, and puri®ed on polyacrylamide gels (71 ± 86 wt, GGTCCCGCCT-CCTTGA and TCAAGGAGGCGGGACC; 71 ± 86 mut 2.2, GGTCCCGGATCCTTGA and TCAAGGATCCGGGACC; 71 ± 86 mut 2.3 GGTCCCGCCGGCTTGA and TCAAGCC-GGCGGGACC).…”

Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4)

“…Tax is a 40 kDa nuclear protein that activates viral transcription through an enhancer element (Tax responsive element: TRE) consisting of three 21 bp repeats located within the HTLV-1 LTR (Sodroski et al, 1984;Felber et al, 1985;Brady et al, 1987;Paskalis et al, 1986). TRE has been further divided into three domains, A, B, and C (Fujisawa et al, 1989;Montagne et al, 1990). The B domain contains a CRE (cyclic AMP response element)-like sequence (TGACG) which is reported to be essential for Tax-mediated transactivation (Fujisawa et al, 1989;Giam and Xu, 1989).…”

The Human T-cell Leukemia Virus-1 Transcriptional Activator Tax Enhances cAMP-responsive Element-binding Protein (CREB) Binding Activity through Interactions with the DNA Minor Groove

“…The core sequence (5Ј-TGACG-3Ј) of the 21-base pair TxRE resembles the cAMPresponsive element (or CRE), the target of the cellular transcriptional regulatory protein CREB (7). The central CRE-like core of each 21-base pair repeat is flanked by GC-rich sequences that are required for Tax transactivation in vivo (2,8,9). The TxRE is a low affinity CREB-binding site in vitro; however, the binding activity of CREB can be dramatically enhanced by the addition of Tax (10 -19).…”