Activation of IL-2 receptor α-chain gene by individual members of the rel oncogene family in association with serum response factor

J. W. Pierce, C. A. Jamieson, J. L. Ross, R. Sen

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of the IL-2Rα gene is regulated by members of the c-Rel/NF- κB family of transcription factors binding to the κB site in the promoter. Previous work has not defined the role of individual members of the c-Rel family in the activation of the IL-2Rα gene. Using the COS cell system, we were able to reconstitute the regulation of the IL-2Rα promoter by expressing cloned Rel family members with serum response factor (SRF). We found that c-rel alone activated the IL-2Rα promoter only weakly but worked with the p50 subunit of NF-κB (NFKB1) to give a higher level of expression. We showed that c-rel heterodimerizes with p50 and the amount of this heterodimer correlated with the level of IL-2Rα gene expression. Our results provide evidence that c-rel/p50 heterodimers activate gene expression in the context of a cellular promoter. We show that c-rel or p65 can cooperate with SRF in the activation of this promoter and the transactivation by c-rel with SRF was enhanced by p50. Synergistic activation required both κB and CArG sites, and binding studies show that these adjacent sites can be occupied simultaneously. The transactivation observed with cloned transcription factors mimics the physiologic induction of the IL-2Rα gene since multiple sequence elements cooperate to give gene activation. The data support the model that c-rel/p50 or p65 can cooperate with SRF to specifically target the expression of the IL-2Rα gene in activated T cells.

Original languageEnglish (US)
Pages (from-to)1972-1980
Number of pages9
JournalJournal of Immunology
Volume155
Issue number4
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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