Differential inducibility of the transcriptional repressor ICER and its role in modulation of Fas ligand expression in T and NK lymphocytes
| Autor: | Josef, Bodor, Jana, Bodorova, Catherine, Bare, Deborah L, Hodge, Howard A, Young, Ronald E, Gress |
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| Rok vydání: | 2002 |
| Předmět: |
Transcriptional Activation
Fas Ligand Protein Transcription Genetic T-Lymphocytes Antigens CD19 CD13 Antigens Cell Line Cyclic AMP Response Element Modulator Jurkat Cells Humans RNA Messenger Promoter Regions Genetic Cells Cultured B-Lymphocytes Binding Sites Membrane Glycoproteins NFATC Transcription Factors Colforsin Nuclear Proteins DNA-Binding Proteins Killer Cells Natural Repressor Proteins Gene Expression Regulation Leukocytes Mononuclear Biomarkers Transcription Factors |
| Zdroj: | European journal of immunology. 32(1) |
| ISSN: | 0014-2980 |
| 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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