HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-kB with other transcription factor families.
The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1) trans-activates both viral and cellular genes. It has previously been shown that granulocyte macrophage-colony stimulating factor (GM-CSF) is constitutively expressed in HTLV-1 infected cells and in cells artificially expressing tax. We show here that the GM-CSF promoter is tax responsive in fibroblasts and T cells, whereas the granulocyte (G)-CSF promoter is tax responsive only in fibroblasts. The tax protein can activate cellular genes through a least two families of transcription factors; the NF-kB/rel and CREB/ATF families. We have used mutant tax proteins to show that the activation of NF-kB proteins is essential for tax trans-activation of both the GM-CSF and G-CSF promoters. The ability of tax to activate CREB/ATF proteins is also essential for GM-CSF transactivation. We have identified a 44 bp region of the GM-CSF promoter that contains tax responsive elements. This region contains a classical NF-kB site, a CK-1 element that can bind the NF-kB p65 protein, as well as a putative ATF binding site. The tax response of the G-CSF promoter requires not only the conserved CK-1 sequence but also an adjacent NF-IL6 binding site that may explain the cell restricted function of the G-CSF promoter.
Himes
S R
SR
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Coles
L S
LS
Katsikeros
R
R
Lang
R K
RK
Shannon
M F
MF
D001483:Base Sequence; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D016355:Genes, pX / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D016328:NF-kappa B; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA