Utilization of signal transduction pathway by the human T-cell leukemia virus type I transcriptional activator tax.
The human T-cell leukemia virus type I (HTLV-I) trans-activator (tax)-inducible enhancer was localized to three copies of 21-base-pair repeats within the long terminal repeat. Interestingly, the TGACG motif found in the center of the 21-base-pair tax-responsive element (TRE) is also present in the cyclic AMP (cAMP)-responsive elements (CREs) and activating transcription factor (ATF)-binding sites. In this study, we demonstrate that the three TRE-binding proteins, TREB-1, TREB-2, and TREB-3, also bind to various CREs and ATF-binding sites and that the TREs can confer upon a heterologous promoter responsiveness to various inducing agents, including tax, cAMP, and E1a. Furthermore, the transcriptional activation of the HTLV-I promoter by tax can be inhibited by several protein kinase inhibitors, including sangivamycin. Our results indicate that the TREs, CREs, and ATF-binding sites are similar cis-acting elements and further suggest (i) that the transcriptional activation of the HTLV-I promoter by tax involves the action of a protein kinase and (ii) that induction by tax, cAMP, and E1a might be mediated by distinct factors or kinases.
Tan
T H
TH
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021-6399.
Jia
R
R
Roeder
R G
RG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017456:Adenovirus Early Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology; D015696:Gene Products, tat; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000502:physiology; D011519:Proto-Oncogenes; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D017456:Adenovirus Early Proteins; D002352:Carrier Proteins; D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D011741:Pyrimidine Nucleosides; D014157:Transcription Factors; C005699:sangivamycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D015056:1-Methyl-3-isobutylxanthine