Document 0291
 DOCN  M9590291
 TI    Transcriptional control of NFKB1 expression.
 DT    9509
 AU    Lambert P; Ludford M; Deacon N; Doherty R; Macfarlane Burnet Centre for
       Medical Research, Fairfield,; Victoria.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:218 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291808
 AB    Optimal expression from the HIV LTR is dependent on binding of proteins
       of the NF-kappa B/Rel family to their cognate motif in the HIV core
       enhancer. NF-kappa B/Rel proteins are transcription factors whose
       translocation from the cytoplasm to the nucleus is induced by cellular
       activating agents such as phorbol esters, TNF-alpha and HTLV-I Tax
       protein. This activation step has been proposed to be one possible
       mechanism mediating the switch from latent to productive HIV infection.
       The NFKB1 gene encodes NFKB1/p50, an important member of the NF-kappa
       B/Rel family whose p105 precursor is itself an important regulatory
       molecule. We were interested in the regulation of the NFKB1 promoter in
       response to activation signals, given the important regulatory
       properties of the gene product. The promoter contains three NF-kappa
       B/Rel binding sites which mediate feedback control; other groups had
       investigated the DNA binding and function of the more 5' two of these in
       the response to activation stimuli. We have used transient transfection
       methods to show that, in Jurkat T cells, the most 3' site is necessary
       for the response of the NFKB1 promoter to HTLV-I Tax. This site is close
       to motifs which resemble the binding sites for the initiator protein,
       HIP-1, and for proteins of the Ets family. We have demonstrated specific
       binding of cellular proteins to the Ets motif, and shown this sequence
       is required for optimal activation of the promoter in response to Tax.
       Cell type-specific binding of proteins to this site may help to explain
       differences between our results using T cells and those of other groups
       using promonocytic cell lines.
 DE    Cell Line  Human  HIV-1/*GENETICS  NF-kappa B/*GENETICS  Promoter
       Regions (Genetics)  T-Lymphocytes/VIROLOGY  Transcription,
       Genetic/*GENETICS  Virus Activation/*GENETICS  MEETING ABSTRACT

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