Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP.
The Tax protein of human T-lymphotropic virus (HTLV)-1 activates expression of the HTLV-1 long terminal repeat through a DNA element that resembles the cellular cyclic AMP-regulated enhancer (CRE). Tax contains a transcriptional activation domain, but its ability to activate gene expression depends on interactions with cellular CRE-binding proteins such as CREB. Whether Tax can activate the expression of cellular CRE-containing genes has been controversial. Here we show that Tax can activate both the HTLV-1 and consensus cellular CREs, and propose that this activation may occur through mechanisms that are differentially dependent on CREB phosphorylation. Tax not only increases the binding of CREB to the viral CRE but also recruits the transcriptional co-activator CBP in a manner independent of CREB phosphorylation. In contrast, association of Tax with the cellular CRE occurs through CBP which, in turn, is recruited only in the presence of phosphorylated CREB.
Kwok
R P
RP
Vollum Institute, Oregon Health Sciences University, Portland 97201 USA.
Laurance
M E
ME
Lundblad
J R
JR
Goldman
P S
PS
Shih
H
H
Connor
L M
LM
Marriott
S J
SJ
Goodman
R H
RH
D001483:Base Sequence; D001665:Binding Sites; D050882:CREB-Binding Protein; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005454:Fluorescence Polarization; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D013004:Somatostatin / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004279:DNA, Viral; D016356:Gene Products, tax; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D013004:Somatostatin; D004247:DNA; D000242:Cyclic AMP; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D017868:Cyclic AMP-Dependent Protein Kinases