Myb protein binds to multiple sites in the human T cell lymphotropic virus type 1 long terminal repeat and transactivates LTR-mediated expression

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

“…For instance, c-Myb, which has been shown to activate basal transcription and inhibit Tax-mediated trans-activation of the LTR, becomes downregulated during monocytic differentiation (Lee et al, 1987;Colgin and Nyborg, 1998). However, this gene has been shown to be upregulated during T cell activation through the IL-2R signaling pathway (Bosselut et al, 1992). The Fos and Jun proteins that form the AP-1 transcriptional complex on the TRE-1 pc repeat, are cell type-speci®c, and are upregulated in a PKC-dependent manner during monocytic differentiation and T cell activation.…”

“…c-Myb binds to six unique sites within the U3 and R regions of the LTR and is activated by signaling through the IL-2R and may provide another link between T cell activation and induction of LTR activation (Bosselut et al, 1992). However, c-Myb is downregulated during monocytic differentiation (Lee et al, 1987), suggesting that LTR transcriptional regulation may be cell-type speci®c.…”

“…HTLV-I basal transcription is greatly enhanced by the virus-encoded regulatory protein Tax, which mediates trans-activation of the HTLV-I LTR by interacting with cellular transcription factors that bind to the three 21 bp repeats within TRE-1, in addition to TRE-2 (Nyborg et al, 1988;Bosselut et al, 1990Bosselut et al, , 1992Nyborg and Dynan, 1990;Muchardt et al, 1992;Zhao and Giam, 1992;Clark et al, 1993;Franklin et al, 1993;Baranger et al, 1995;Brauweiler et al, 1995;Fujii et al, 1995;Barnhart et al, 1997;Lenzmeier and Nyborg, 1997;Reddy et al, 1997;Yan et al, 1998;Goren et al, 1999;Van Orden et al, 1999;Mick et al, 2000;Scoggin et al, 2001). Initially, it was thought that Tax did not interact directly with Tax-responsive sequences within the LTR, but instead trans-activated viral transcription by interacting with cellular transcription factors that directly interact with the TREs (Baranger et al, 1995;Perini et al, 1995;Giebler et al, 1997).…”

“…In addition, HTLV-I transcription is also dependent on a second enhancer element designated as Tax-responsive element 2 (TRE-2) located between the pc and pp repeats from À163 to À117 Tanimura et al, 1993). Numerous transcription factors have been shown by footprinting and electrophoretic mobility shift analyses to bind to TRE-2 Sp1/Sp3 including Ets factors (Ets-1, Ets-2, Elf-1, p-ets, and TIF-1), and c-Myb (Bosselut et al, 1990(Bosselut et al, , 1992Clark et al, 1993;Colgin and Nyborg, 1998;Torgeman et al, 1999). NF-kB, AP-2, PU.1, NHF-3, and PEA-3 transcription factors have been proposed to also interact with this region based on sequence analysis (Datta et al, 2000), but further experimentation will be required to determine if these cellular factors physically interact with this region.…”

T-Cell Receptor/CD28 Engagement When Combined with Prostaglandin E2Treatment Leads to Potent Activation of Human T-Cell Leukemia Virus Type 1

“…The tax gene product can also affect expression of a large array of cellular and viral genes (7,24,69,76). A wide variety of cellular factors interact with the promoter region of HTLV-1 localized in the long terminal repeat (LTR), such as members of the cAMP response element-binding protein (CREB)/activation transcription factor family, TIF, THP, HEBI, TFIID, SP1, and others (6,8,18,39,46,52,55,77,83). Tax does not bind to the HTLV-1 LTR region directly but rather associates via protein-protein interactions with cellular proteins associated with the viral promoter (13,26,45,84).…”