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M9610245.TXT
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1996-01-30
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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).