Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp - PubMed (original) (raw)

Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp

E Y Tsai et al. Mol Cell Biol. 1996 Feb.

Abstract

The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest genes expressed upon the activation of a T or B cell through its antigen receptor. Previous experiments have demonstrated that in stimulated T cells, a TNF-alpha promoter element, kappa 3, which binds NFATp, is required for the cyclosporin A-sensitive transcriptional activation of the gene. Here, we demonstrate that a cyclic AMP response element (CRE), which lies immediately upstream of the kappa 3 site, is also required for induction of TNF-alpha gene transcription in T cells stimulated by calcium ionophore or T-cell receptor ligands. The CRE binds ATF-2 and Jun proteins in association with NFATp bound to kappa 3. These proteins bind noncooperatively in vitro; however, the transcriptional activity of the CRE/kappa 3 composite site is dramatically higher than the activity of the kappa 3 site alone, indicating that the two sites cooperate in vivo. This study is the first demonstration of a role for ATF-2 in TNF-alpha gene transcription and of a functional interaction between ATF-2/Jun and NFATp. This novel pairing of NFATp with ATF-2/Jun may account for the specific and immediate pattern of TNF-alpha gene transcription in stimulated T cells.

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References

1. Trends Genet. 1990 Mar;6(3):69-72 - PubMed
1. J Biol Chem. 1992 Nov 5;267(31):22102-7 - PubMed
1. Mol Cell Biol. 1994 Oct;14(10):6464-75 - PubMed
1. J Biol Chem. 1994 Nov 11;269(45):28181-6 - PubMed
1. J Biol Chem. 1994 Dec 2;269(48):30445-50 - PubMed

Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp - PubMed (original) (raw)