Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3.
Tax, a protein encoded by the env-pX gene of human T-cell leukemia virus type I (HTLV-I), interacts with various host cell transcription factors. Tax activates transcription from the long terminal repeat (LTR) of HTLV-I through association with cyclic AMP-responsive element-binding protein (CREB). Here, we present evidence that transducer of regulated cyclic AMP-response element-binding protein 3 (TORC3), a co-activator of CREB, is involved in Tax-induced transcriptional activation from the HTLV-I LTR. By using a luciferase assay system, we show that TORC3 alone can enhance transcription from the HTLV-I LTR, as well as from a cellular cyclic AMP-response element (CRE). Interestingly, we find that co-expression of TORC3 and Tax dramatically increased transcriptional activation at the HTLV-I LTR. We also show by glutathione S-transferase pull-down and co-immunoprecipitation experiments that TORC3 interacts with Tax. Using deletion mutant analysis, we identify the Tax interaction domain of TORC3 as a region spanning from amino acid 1 to 103, which contains a coiled-coil domain. These results provide important clues toward understanding the molecular mechanism of Tax-dependent transcriptional activation of the HTLV-I LTR.
Koga
Hiroshi
H
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Ohshima
Takayuki
T
Shimotohno
Kunitada
K
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D016356:Gene Products, tax / Q000378:metabolism*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020079:Terminal Repeat Sequences; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
C495791:CRTC3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D016356:Gene Products, tax; D015534:Trans-Activators; D014157:Transcription Factors; D000242:Cyclic AMP; D008156:Luciferases; D005982:Glutathione Transferase