HTLV-1 21 bp repeat sequences facilitate stable association between Tax and CREB to increase CREB binding affinity

Journal of Molecular Biology
M J Yin, R B Gaynor

Abstract

The human T-cell leukemia virus type I (HTLV-I) transactivator protein Tax is critical for the activation of viral gene expression and the transformation of T-lymphocytes. Tax activation of HTLV-I gene expression is mediated by three highly homologous regulatory elements known as 21 bp repeats which bind the transcription factor CREB. Questions remain about the mechanism by which Tax can stimulate CREB binding, whether Tax alters CREB binding affinity, what specific sequences in the HTLV-I 21 bp repeat mediate ternary complex formation, and if the ternary complex comprised of Tax and CREB can recruit coactivators such as CBP. To address these points, we used immobilized templates containing either the HTLV-I 21 bp repeats or the somatostatin CRE to assay Tax association with ATF/CREB family members. Tax formed a stable ternary complex on each of the 21 bp repeats with the transcription factor CREB but not related ATF/CREB proteins. In contrast, Tax did not form a similar complex on the CREB binding site in the somatostatin promoter. The formation of this complex was dependent on 3' sequences flanking the CREB binding site within each of the 21 bp repeats and resulted in marked increases in CREB association and binding affinity....Continue Reading

Citations

Jan 23, 1998·Nature Structural Biology·Y Q ChenG Ghosh
Mar 22, 2002·Journal of Virology·Min-Hui LiangChou-Zen Giam
Jan 1, 1997·Annual Review of Genetics·J Flint, T Shenk
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Dec 16, 1998·The Journal of Biological Chemistry·F KashanchiJ N Brady
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Oct 17, 1998·Methods : a Companion to Methods in Enzymology·F Bex, R B Gaynor

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