Differential inducibility of the transcriptional repressor ICER and its role in modulation of Fas ligand expression in T and NK lymphocytes

Autor: Howard A. Young, Jana Bodorova, Catherine V. Bare, Ronald E. Gress, Deborah L. Hodge, Josef Bodor
Rok vydání: 2002
Předmět:
Zdroj: European Journal of Immunology. 32:203-212
ISSN: 1521-4141
0014-2980
DOI: 10.1002/1521-4141(200201)32:1<203::aid-immu203>3.0.co;2-c
Popis: The engagement of antigen receptor can initiate apoptosis of T lymphocytes through the induced expression of Fas ligand (FasL). Forskolin, an activator of the cAMP/PKA pathway, results in antagonism of Fas-dependent, activation-induced cell death (AICD) by suppressed expression of the FasL. We report that forskolin-mediated induction of inducible cAMP early repressor (ICER) correlates with transcriptional attenuation of FasL expression in the AICD model 2B4 T cell hybridoma. ICER is inducible in human peripheral blood CD3 + T cells, but in CD19 + B cells, its induction is less responsive to forskolin treatment. Increased expression of ICER correlates with decreased FasL expression in both T and NK cells. ICER binds specifically to the proximal DNA binding site of the nuclear factor of activated T cells (NFAT) in the FasL promoter and in the presence of the minimal NFAT DNA-binding domain, the proximal NFAT motif allows ICER and NFAT to form an NFAT/ICER ternary complex in vitro. Moreover, in the activated 2B4 T cell hybridoma, the proximal NFAT motif participates in the down-regulation of the FasL promoter mediated by ICER. These findings provide further insight into the mechanism involved in cAMP-mediated transcriptional attenuation of FasL expression in T and NK lymphocytes.
Databáze: OpenAIRE
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