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Molecular and Cellular Biology, July 2001, p. 4515-4527, Vol. 21, No. 14
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.14.4515-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Novel CD28-Responsive Enhancer Activated by
CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor
-Chain Locus
Jung-Hua
Yeh,1
Patrick
Lecine,1
Jacques A.
Nunes,1
Salvatore
Spicuglia,2
Pierre
Ferrier,2
Daniel
Olive,1 and
Jean
Imbert1,*
INSERM U119-IFR57, 13009 Marseilles,1 and Centre d'Immunologie
CNRS-INSERM-Univ.Med., 13288 Marseille Cedex
09,2 France
Received 20 December 2000/Returned for modification 13 February
2001/Accepted 16 April 2001
The interaction of interleukin-2 (IL-2) with its receptor (IL-2R)
critically regulates the T-cell immune response, and the
chain
CD25/IL-2R
is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2R
gene is
regulated by at least three positive regulatory regions (PRRI, PRRII,
and PRRIII), but none responded to CD28 engagement in gene reporter
assays although CD28 costimulation strongly amplifies IL-2R
gene
transcription. By DNase I hypersensitivity analysis, we have identified
a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb
5' of the IL-2R
gene. PRRIV/CD28rE contains a functional CRE/TRE
element required for CD28 signaling. The T-cell-specific,
CD28-responsive expression of the IL-2R
gene appears controlled
through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family
transcription factors.
*
Corresponding author. Mailing address: INSERM
U119-IFR57, 27 Blvd. Lei Roure, 13009 Marseilles, France. Phone: 33 (0)491 75 84 04. Fax: 33 (0)491 26 03 64. E-mail:
imbert{at}marseille.inserm.fr.
Molecular and Cellular Biology, July 2001, p. 4515-4527, Vol. 21, No. 14
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.14.4515-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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