Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences.
One potent transcriptional activator of human T-cell leukemia virus type I (HTLV-I) is virally encoded protein Tax (p40x). p40x trans-activates HTLV-I through the long terminal repeat (LTR) by using a triply repeated 21-base-pair sequence as the target. In this report we have characterized the induction of the HTLV-I LTR by 12-O-tetradecanoylphorbol-13-acetate (TPA). By assaying progressively deleted mutations in the HTLV-I LTR, we have delimited a 60-base-pair sequence in the LTR which is capable of conferring TPA responsiveness, but not p40x responsiveness, to heterologous promoters in a position-independent fashion. This HTLV-I TPA-responsive element is specifically recognized by preexisting factors from uninfected cells. We show that activation of this sequence by phorbol ester does not require de novo cellular protein synthesis. When the HTLV-I LTR was simultaneously activated by both Tax and TPA, an additive effect was seen. This suggests the use of distinct regulatory pathways by the two respective trans-activators.
Radonovich
M
M
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Jeang
K T
KT
D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects*; D015486:HTLV-I Antigens / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D015486:HTLV-I Antigens; D015534:Trans-Activators; D014157:Transcription Factors; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate