Article

Functional and biochemical interaction of the HTLV-I Tax1 transactivator with TBP

Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure de Lyon, UMR 49, CNRS, France.
The EMBO Journal (Impact Factor: 10.43). 12/1993; 12(11):4269-78.
Source: PubMed

ABSTRACT

The human T-cell leukemia virus type I (HTLV-I) codes for the potent transcriptional activator, Tax1, which induces the enhancer activity of various enhancer elements. In the case of the 21 bp enhancer of the HTLV-I provirus, this induction is correlated with the association of Tax1 with this DNA element via a specific cellular factor. That the indirect association of Tax1 with DNA can lead to transcriptional activation has also been supported by the study of chimeric GAL4-Tax1 proteins. The GAL4-Tax1 stimulatory effect exhibits a strong self-squelching. In order to determine whether Tax1 interacts directly with the general transcription factors or via intermediary molecules, we have analyzed how overexpression of the TATA binding protein (TBP) and TFIIB protein affects the squelching curve of GAL4-Tax1. The data presented here show that overexpression of TBP strongly increases the stimulatory effect of GAL4-Tax1, causes a displacement of the maximum of the squelching curve and partially alleviates the squelching. Under similar conditions TFIIB exhibited little effect. From these results we conclude that Tax1 can increase the recruitment of TBP by directly interacting with this protein. Biochemical experiments with purified proteins produced in bacteria confirmed that Tax1 can interact with TBP but not with TFIIB. Tax1 interacts with the conserved C-terminal part of TBP. Analysis of the ability of different mutants of Tax1 fused to the GAL4 DNA binding domain to activate transcription and to associate with TBP, showed that these activities are correlated. However, since one transcriptionally inactive mutant was able to interact efficiently with TBP in vitro, it would appear that an event other than the Tax1-TBP contact also intervenes in the activation of transcription by Tax1.

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    • "Tax, a non-structural protein and the main driver of viral transcription, potently activates viral transcription during the early phase of infection by recruiting multiple cellular transcription factors[54]. Three conserved 21-bp repeat elements, known as the Tax-responsive element 1 (TRE-1), bind the cyclic AMP response element binding protein (CREB) at the TRE-1 site through its N-terminus (NTD)55565758596061, while the C-terminal domain (CTD) of Tax is believed to promote the transcriptional initiation and RNA polymerase elongation by directly interacting with the TATA binding protein[5,62]. The Tax-CREB promoter complex recruits the multifunctional cellular coactivators CREB binding protein (CBP), p300, and the p300/CBP-associated factor to the LTR636465666768. "
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    • "Another mechanism by which HTLV-1 may influence the host cell miRNA expression profile is through the activation of host transcription factors. Important transcription factors and cellular kinases which interact directly with the viral protein Tax are CREB, serum-responsive factor (SRF), NFκB , Cyclins D2 and D3, mitotic check point regulators (MAD1), cyclin dependent kinases (CDKs), the CDK inhibitors p16 INK4A and p21 (WAF1/CIP1) , and the tumor suppressor p53 (Caron et al., 1993; Suzuki et al., 1994; Yin et al., 1995, 1998; Clemens et al., 1996; Colgin and Nyborg, 1998; Harrod et al., 1998; Gachon et al., 2000; Nicot et al., 2000; Xiao et al., 2001; Kashanchi and Brady, 2005; Easley et al., 2010). In particular, the NF-κB pathways activation is a hall mark of HTLV-1 infection and may be the result of direct interaction between Tax and the NF-κB regulatory subunit IKKγ (Sun and Yamaoka, 2005; Yasunaga and Matsuoka, 2011). "
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