Characterization of the constitutive and inducible components of a T cell IL-4 activation responsive element

D. Tara, D. L. Weiss, M. A. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

An IL-4 regulatory element, activation responsive element (ARE), located between -88 and -60, contributes to activation-dependent transcription of IL- 4/CAT reporter gene constructs in T cells. It was previously demonstrated that nuclear proteins present in both unstimulated and stimulated T cells specifically interact with the ARE. In this study, these proteins were further characterized. UV cross-linking experiments established that multiple proteins are associated with the ARE in both the constitutive and activation- dependent complexes and several of these have identical apparent m.w. The formation of both complexes is dependent on the same ARE subsequence. In addition, activator protein 1 family members are uniquely associated with the activation-dependent complex. These results support a model in which activation-dependent proteins, including jun/fos family members, associate with a preexisting transcription complex to influence inducible IL-4 gene transcription. The ARE shares 9 bp of sequence identity with the IL-2 nuclear factor of activated T cell (NF-AT) binding site within the critical protein binding region, and several features of ARE-protein interactions are similar to the NF-AT transcription complex. However, we demonstrate that the constitutive nuclear ARE-associated factors react with Abs, raised to NF- AT(p) and NF-AT(c), preferentially bind to the ARE but not to the NF-AT binding site and are cyclosporin A sensitive. Taken together, these data indicate that there are IL-4 gene-specific factors associated with the ARE and that the formation of the ARE and NF-AT complexes are regulated differently.

Original languageEnglish (US)
Pages (from-to)4592-4602
Number of pages11
JournalJournal of Immunology
Volume154
Issue number9
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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