Stress-Induced Fas Ligand Expression in T Cells Is Mediated through a MEK Kinase 1-Regulated Response Element in the Fas Ligand Promoter
| Autor: | Gary A. Koretzky, Kevin M. Latinis, Stephan J. Kempiak, Andre E. Nel, Mary Faris |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Fas Ligand Protein
Ultraviolet Rays Recombinant Fusion Proteins T-Lymphocytes Response element MAP Kinase Kinase Kinase 1 Protein Serine-Threonine Kinases Transfection Jurkat cells Polymerase Chain Reaction Fas ligand Jurkat Cells Genes Reporter Stress Physiological Gene expression Consensus Sequence Humans Luciferases Promoter Regions Genetic Molecular Biology Transcription factor Cell Growth and Development Sequence Deletion Binding Sites Membrane Glycoproteins biology Base Sequence Kinase Cell Biology Molecular biology Activating transcription factor 2 Enzyme Activation Apoptosis Gamma Rays Enzyme Induction biology.protein Cytokines |
| Popis: | T lymphocytes undergo apoptosis in response to a variety of stimuli, including exposure to UV radiation and gamma-irradiation. While the mechanism by which stress stimuli induce apoptosis is not well understood, we have previously shown that the induction of Fas ligand (FasL) gene expression by environmental stress stimuli is dependent on c-Jun N-terminal kinase (JNK) activation. Using inducible dominant-active (DA) JNK kinase kinase (MEKK1) expression in Jurkat cells, we map a specific MEKK1-regulated response element to positions -338 to -316 of the Fas ligand (FasL) promoter. Mutation of that response element abrogated MEKK1-mediated FasL promoter activation and interfered in stress-induced activation of that promoter. Using electrophoretic mobility shift assays, we demonstrate that activator protein 1 (AP-1) binding proteins, namely, activating transcription factor 2 (ATF2) and c-Jun, bind to the MEKK1 response element. Transient transfection of interfering c-Jun and ATF2 mutants, which lack the consensus JNK phosphorylation sites, abrogated the transcriptional activation of the FasL promoter, demonstrating the involvement of these transcription factors in the regulation of the FasL promoter. Taken together, our data indicate that MEKK1 and transcription factors regulated by the JNK pathway play a role in committing lymphocytes to undergo apoptosis by inducing FasL expression via a novel response element in the promoter of that gene. |
| Databáze: | OpenAIRE |
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