Document 0245
 DOCN  M9610245
 TI    Novel NFAT sites that mediate activation of the interleukin-2 promoter
       in response to T-cell receptor stimulation.
 DT    9601
 AU    Rooney JW; Sun YL; Glimcher LH; Hoey T; Department of Genetics, Harvard
       Medical School, Boston,; Massachusetts 02115, USA.
 SO    Mol Cell Biol. 1995 Nov;15(11):6299-310. Unique Identifier : AIDSLINE
       MED/96026011
 AB    The transcription factors NFAT and AP-1 have been shown to be essential
       for inducible interleukin-2 (IL-2) expression in activated T cells. NFAT
       has been previously reported to bind to two sites in the IL-2 promoter:
       in association with AP-1 at the distal antigen response element at -280
       and at -135. On the basis of DNase I footprinting with recombinant NFAT
       and AP-1 proteins, gel shift assays, and transfection experiments, we
       have identified three additional NFAT sites in the IL-2 promoter.
       Strikingly, all five NFAT sites are essential for the full induction of
       promoter activity in response to T-cell receptor stimulation. Four of
       the five NFAT sites are part of composite elements able to bind AP-1 in
       association with NFAT. These sites display a diverse range of
       cooperativity and interdependency on NFAT and AP-1 proteins for binding.
       One of the NFAT sites directly overlaps the CD28-responsive element. We
       present evidence that CD28 inducibility is conferred by the AP-1
       component in NFAT-AP-1 composite elements. These findings provide
       further insight into the mechanisms involved in the regulation of the
       IL-2 promoter.
 DE    Animal  Antigens, CD28/PHYSIOLOGY  Base Sequence  Binding Sites  Cell
       Line  Cell Nucleus/METABOLISM  DNA Footprinting  DNA-Binding
       Proteins/*METABOLISM  Interleukin-2/*GENETICS  Lymphocyte Transformation
       Mice  Molecular Sequence Data  Oligodeoxyribonucleotides/CHEMISTRY
       *Promoter Regions (Genetics)  Receptors, Antigen, T-Cell/*PHYSIOLOGY
       Signal Transduction  Support, Non-U.S. Gov't  Th1 Cells/*PHYSIOLOGY
       Transcription Factor AP-1/*METABOLISM  Transcription Factors/*METABOLISM
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).