Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes.
Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.
Fujii
M
M
Department of Molecular Virology and Oncology, Kanazawa University, Ishikawa, Japan.
Tsuchiya
H
H
Chuhjo
T
T
Akizawa
T
T
Seiki
M
M
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D004926:Escherichia coli / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D016762:Genes, fos; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D026362:Serum Response Factor; D015398:Signal Transduction; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C497326:EGR2 protein, human; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D016356:Gene Products, tax; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D005982:Glutathione Transferase