Transforming Growth Factor Beta and Cyclosporin A Inhibit the Inducible Activity of the Interleukin-2 Gene in T Cells Through a Noncanonical Octamer-binding Site

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Feb 1

PMID 8423782

Citations 58

Authors

T Brabletz

I Pfeuffer

E SCHORR

F Siebelt

T Wirth

E Serfling

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor beta (TGF-beta) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-beta on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (proto-enhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-beta-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and AP-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-beta and cyclosporin A in El4 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.

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