FUNCTIONAL INTERACTION OF THE HTLV-1 TRANSACTIVATOR TAX WITH ACTIVATING TRANSCRIPTION FACTOR-IV (ATF4)

The Tax protein of the Human T-cell Leukemia Virus (HTLV) activates th e expression of viral mRNA through a three 21 bp repeat enhancer locat ed within the HTLV-1 LTR, Since Tax does not bind to the 21bp DNA repe ats directly, it has been speculated that Tax interacts with cellular protein(s) which mediate binding to the enhancer, We employed the yeas t two hybrid system to identify host proteins that are potentially rel evant to Tax transactivation. We identified a Tax binding protein enco ded from a cDNA expression library derived from peripheral blood lymph ocytes. The corresponding cDNA has sequence identity with a known tran scription factor, activating factor-4 (ATF-4). ATF-4 also binds to GST -Tax fusion protein in vitro. Tax mutants that did not transactivate t he HTLV-1 LTR also failed to bind ATF-4. The critical domain for Tax b inding resides in a 85 amino acid stretch in the C-terminus of ATF-4, which contains the basic domain and leucine zipper, We further demonst rated that both full length and N-terminal truncated ATF-4 were able t o enhance Tax transactivation, Thus, ATF-4 may act as an adapter betwe en Tax and the TRE (Tax responsive element), and play an important rol e in Tax-mediated transactivation.