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PMID: 11416131 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Novel CD28-responsive enhancer activated by CREB/ATF and AP-1 families in the human interleukin-2 receptor alpha-chain locus.

Molecular and cellular biology ·Vol. 21 ·No. 14 ·2001-07-00 ·Pages 4515-27

Yeh JH, Lecine P, Nunes JA, Spicuglia S, Ferrier P, Olive D, Imbert J

Abstract

The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the alpha chain CD25/IL-2Ralpha is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Ralpha 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-2Ralpha 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-2Ralpha gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Ralpha gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.

MeSH Terms
Activating Transcription Factors Animals Base Sequence Blood Proteins/metabolism CD28 Antigens/metabolism COS Cells Chlorocebus aethiops Cyclic AMP Response Element-Binding Protein/metabolism DNA, Complementary Enhancer Elements, Genetic Humans Jurkat Cells Molecular Sequence Data Receptor-CD3 Complex, Antigen, T-Cell/metabolism Receptors, Interleukin-2/genetics Regulatory Sequences, Nucleic Acid Transcription Factor AP-1/metabolism Transcription Factors/metabolism Transcriptional Activation
Chemicals
Activating Transcription Factors Blood Proteins CD28 Antigens Cyclic AMP Response Element-Binding Protein DNA, Complementary Receptor-CD3 Complex, Antigen, T-Cell Receptors, Interleukin-2 Transcription Factor AP-1 Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yeh J H
INSERM U119-IFR57, 13009 Marseilles, France.
Lecine P
Nunes J A
Spicuglia S
Ferrier P
Olive D
Imbert J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.14.4515-4527.2001
Published
2001-07-00
Pages
4515-27
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC87111
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.14.4515-4527.2001 PMC Full Text View journal details
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