Transactivation by the human T-cell leukemia virus Tax protein is mediated through enhanced binding of activating transcription factor-2 (ATF-2) ATF-2 response and cAMP element-binding protein (CREB).
The human T-cell leukemia virus type I (HTLV-I)-encoded transcriptional activator protein Tax is strongly implicated in HTLV-I pathogenesis. Tax regulates HTLV-I gene expression through three 21-base pair (bp) repeat enhancer elements located in the transcriptional control region of the virus. Tax does not bind these elements directly, but mediates transactivation through the cellular transcription factors that recognize a cAMP response element (CRE)-like sequence centered within each of the 21-bp repeats. In this report, we identify activating transcription factor-2 (ATF-2) and CRE-binding protein (CREB) as the principal T-cell proteins that bind the three 21-bp repeats in vitro. Purified Tax protein augments the level of RNA synthesis induced by ATF-2 and CREB in a cell-free transcription assay, providing evidence that Tax cooperates with these cellular proteins to activate HTLV-I transcription. Furthermore, Tax dramatically increases the binding of both the T-cell-derived and recombinant forms of ATF-2 and CREB to each of the 21-bp repeats. The target sequences for this enhancement reside within the DNA binding/dimerization domains of these proteins. These data suggest that Tax transactivates HTLV-I gene expression by increasing the number of bound ATF-2 and CREB molecules at the viral promoter.
Franklin
A A
AA
Department of Biochemistry, Colorado State University, Fort Collins 80523.
Kubik
M F
MF
Uittenbogaard
M N
MN
Brauweiler
A
A
Utaisincharoen
P
P
Matthews
M A
MA
Dynan
W S
WS
Hoeffler
J P
JP
Nyborg
J K
JK
D051698:Activating Transcription Factor 2; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002846:Chromatography, Affinity; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors