The indirect association of human T-cell leukemia virus tax protein with DNA results in transcriptional activation

Abstract

trans-activator p40 of human T-cell leukemia virus type I activates specific enhancers and stimulates transcription of the viral and some cellular genes but does not bind directly to the enhancer sequences. We demonstrated here that a fusion protein of p4Ot^l and GAL4 DNA binding domain activated transcription dependent on the GAL4-binding site in the reporter plasmid. Mutants of p40 were also tested in the fusion protein, and their activities were found to be in parallel with those of their free forms on the original target long terminal repeat. This activation with GAL4 fusion protein was interfered with by the free form of p4Ot. These results suggest that p4Ofax associates with DNA through interaction with DNA binding protein(s) and also interacts with another transcription factor(s) to elicit the activation. Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (25, 37). Replication of HTLV-I is regulated at transcriptional (2, 6, 28, 32) and posttranscriptional (9, 11, 12) levels by its own products, TAX and REX, respectively. The tax gene product, p4fax,

Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins

“…The deletion findings are in agreement with those of others (10,13), who have shown that deletions in Tax were generally inactivating for function. This class of mutations represents changes that either were structurally disruptive or affected a common domain necessary for activating both LTRs.…”

The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression

“…According to several recent reports, Tax could stimulate viral transcription through enhancement of the DNA binding of CREB and ATF-2 to the 21-bp repeat (2,3,5,21,50,61,68,73,81). Others studies suggest that Tax could act through direct anchoring to the promoter via protein-protein interactions with the bound ATF/CREB proteins (14,22,23,71). Finally, Brauweiler et al (11) have recently provided evidence that Tax could stabilize the binding of CREB (but not ATF-2) to the 21-bp repeats.…”

Two mechanisms in the action of repressor δEF1: binding site competition with an activator and active repression

“…The cDNA fragment encompassing the NR domain (1-493) was amplified by PCR and inserted into the pGal-BL (Fujisawa et al 1991) to obtain the effector expression vector pGal-NR. The reporter pG4-TK-Luc was constructed by inserting 4 copies of Gal4 binding sequence (gift of J. Fujisawa) into pTK-Luc which carries the promoter region of HSV-thymidine kinase gene (-197 -þ56).…”