Journal article
CCAAT/enhancer-binding proteins modulate human T cell leukemia virus type 1 long terminal repeat activation
Journal of neurovirology, Vol.12, pp.65-65
01 May 2006
Abstract
CCAAT/enhancer-binding protein (C/EBP) basic region/leucine zipper (bZIP) transcription factors have been shown to form heterodimers with cAMP-responsive element binding protein 2 (CREB-2), a bZIP transcription factor involved in regulating basal and Tax-mediated transactivation of the human T cell leukemia virus type 1 (HTLV-1) long terminal repeat (LTR). The interaction between C/EBPbeta or C/EBPzeta with CREB-2 has been previously shown to down-regulate Tax-mediated transactivation of the HTLV-1 LTR. In cells of the monocyte/macrophage lineage (proposed to play a role in HTLV-1 pathogenesis as an accessory target cell population), several members of the C/EBP family including C/EBPbeta are expressed at high levels. Therefore, the functional impact of C/EBP factor expression on both basal and Tax-mediated transactivation of the HTLV-1 LTR was examined. Low-level basal activation of the HTLV-1 LTR was significantly enhanced by overexpression of C/EBPbeta, C/EBPdelta, or C/EBPepsilon, whereas transactivation of the HTLV-1 LTR by Tax was inhibited by overexpression of C/EBPalpha and C/EBPbeta, and to a lesser extent C/EBPdelta. Inhibition of Tax-mediated transactivation of the HTLV-1 LTR was co-activator-independent and did not require binding of C/EBP to the Tax-responsive elements of the viral promoter. Deletion of the C-terminal leucine zipper dimerization domain or the basic region DNA binding domain of C/EBPbeta blocked C/EBPbeta from inhibiting Tax-mediated transactivation of the HTLV-1 LTR, suggesting that C/EBP dimerization (likely to CREB-2) may be critical for down-regulating Tax-mediated transactivation of the HTLV-1 LTR. Therefore, endogenous expression of C/EBPalpha and C/EBPbeta (which are primarily limited to myeloid lineage cells) may be critical factors limiting viral gene expression in cells of monocyte/macrophage lineage.
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Details
- Title
- CCAAT/enhancer-binding proteins modulate human T cell leukemia virus type 1 long terminal repeat activation
- Creators
- D PandyaC GrantM NonnemacherP JainB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.12, pp.65-65
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170133304721