Differential activation of the 21-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP.
A transcriptional trans-acting factor p40tax of human T-cell leukemia virus type I (HTLV-I) functions as an inducer for expression of HTLV-I provirus via activation of the enhancer in the long terminal repeat of HTLV-I. In addition to p40tax and a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, we report here that forskolin, an activator of adenyl cyclase, also induces function of the HTLV-I enhancer. Experiments with mutants of the HTLV-I enhancer revealed that TPA-induced activation was not mediated by solely a 21-base-pair (bp) sequence that is repeated three times in the enhancer, whereas the 21-bp enhancer element can act as a sufficient cis-acting sequence for activation by both p40tax and forskolin. In addition, we found that nuclear factor(s) like the cyclic AMP-responsive element (CRE) binding factor could bind to the HTLV-I 21-bp enhancer element. However, a difference was found in sequences required for activation by p40tax and forskolin. A CRE related sequence present in the 21-bp enhancer element was enough for forskolin-induced activation. On the other hand, p40tax required a much longer sequence that is overlapping but not identical to the CRE related sequence, suggesting that the forskolin-induced cyclic AMP pathway may be partly involved in, but not sufficient for p40tax-mediating trans-activation of the HTLV-I enhancer.
Nakamura
M
M
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Niki
M
M
Ohtani
K
K
Sugamura
K
K
D001482:Base Composition; D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D015486:HTLV-I Antigens / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D015486:HTLV-I Antigens; D015534:Trans-Activators; D014157:Transcription Factors; D002104:Cadmium; D005576:Colforsin; D000242:Cyclic AMP; D019256:Cadmium Chloride; D013755:Tetradecanoylphorbol Acetate