κB Site-Dependent Activation of the Interleukin-2 Receptor α-Chain Gene Promoter by Human c-Rel

Tse Hua Tan, Grace P. Huang, Antonio Sica, Paritosh Ghosh, Howard A. Young, Dan L. Longo, Nancy R. Rice

Research output: Contribution to journalArticlepeer-review

Abstract

The cis-acting control elements of the interleukin-2 receptor α-chain (IL-2Rα) gene contain a potent κB-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the κB-binding protein NF-κB complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2Rα transcription. We now demonstrate that the recombinant human c-Rel protein binds to the κB element in the IL-2Rα promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2Rα promoter, but not the κB-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the κB site of the IL-2Rα promoter. Finally, induction of surface IL-2Rα expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2Rα κB site. Our study identified c-Rel as one component of the Rel/NF-κB-family proteins involved in the κB-dependent activation of IL-2Rα gene expression. Furthermore, our results suggest that a RelNA-like cellular factor (e.g., NF-κB p50 or p49 subunit) acts in synergy with c-Rel during T-cell activation.

Original languageEnglish
Pages (from-to)4067-4075
Number of pages9
JournalMolecular and Cellular Biology
Volume12
Issue number9
Publication statusPublished - Sep 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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