Involvement of NF-AT in type I human T-cell leukemia virus tax-mediated fas ligand promoter transactivation

Isis Rivera, Edward W. Harhaj, Shao Cong Sun

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32 Scopus citations

Abstract

Human T-cell leukemia virus type I (HTLV-I)-infected T-cells constitutively express surface Fas ligand (FasL), which may serve as a mechanism of viral pathogenesis. HTLV-I induces transcription of FasL gene through the vital transactivator Tax, although the underlying molecular mechanism remains unclear. In the present study, we have analyzed both the cis-activating element and transactivating factors involved in Tax activation of the FasL promoter. We show that the 486-base pair upstream region of the human FasL gene is sufficient for Tax-mediated transactivation in Jurkat T- cells. Interestingly, a palindromic DNA sequence (GGAAACTTCC) covering the consensus NF-ATp binding site (GGAAA), is required for Tax activation of FasL promoter. The involvement of NF-AT in this transactivation event is suggested by the finding that Tax fails to activate the FasL promoter in a Jurkat T- cell line defective in capacitative calcium entry, a signaling mechanism involved in NF-AT activation. Furthermore, activation of FasL promoter by Tax is largely attenuated in the nonlymphoid F9 embryonal and COS kidney cells deficient in NF-ATp expression. DNA-protein interaction assays reveal that the NF-AT-like motif in the FasL promoter is bound by both NF-ATp and NF-AT4 in Jurkat T-cells expressing Tax. The binding of NF-ATp, although not NF- AT4, to this enhancer also occurs along with HTLV-I-mediated infection of human peripheral blood T-cells. Furthermore, exogenously transfected NF-ATp binds to the NF-AT-like enhancer and participates in Tax-mediated FasL promoter transactivation. These results suggest an important role for proteins of the NF-AT family in HTLV-I Tax-mediated FasL gene transactivation.

Original languageEnglish (US)
Pages (from-to)22382-22388
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number35
DOIs
StatePublished - Aug 28 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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