Cot kinase induces cyclooxygenase-2 expression in T cells through activation of the nuclear factor of activated T cells
| Autor: | Susana Alemany, Rosa de Gregorio, Miguel A. Iñiguez, Manuel Fresno |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
T-Lymphocytes Mitogen-activated protein kinase kinase Biochemistry Gene Expression Regulation Enzymologic Transactivation Jurkat Cells Proto-Oncogene Proteins Humans Protein kinase A Promoter Regions Genetic Molecular Biology DNA Primers biology MAP kinase kinase kinase Base Sequence NFATC Transcription Factors Chemistry Cyclin-dependent kinase 5 Calcineurin Cyclin-dependent kinase 2 Membrane Proteins Nuclear Proteins NFAT Cell Biology MAP Kinase Kinase Kinases Molecular biology Up-Regulation DNA-Binding Proteins Isoenzymes Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Cancer research Cyclin-dependent kinase 9 Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 276(29) |
| ISSN: | 0021-9258 |
| Popis: | Cyclooxygenase-2 (COX-2) is induced in human T lymphocytes upon T cell receptor triggering. Here we report that Cot kinase, a mitogen-activated protein kinase kinase kinase involved in T cell activation, up-regulates COX-2 gene expression in Jurkat T cells. Induction of COX-2 promoter activity by Cot kinase occurred mainly through activation of the nuclear factor of activated T cells (NFAT). Mutation of the distal (−105/−97) and proximal (−76/−61) NFAT response elements in the COX-2 promoter abolished the activation induced by Cot kinase. Even more, coexpression of a dominant negative version of NFAT inhibited Cot kinase-mediated COX-2 promoter activation, whereas cotransfection of a constitutively active version of the calcium-dependent phosphatase calcineurin synergizes with Cot kinase in the up-regulation of COX-2 promoter-driven transcription. Strikingly, Cot kinase increased transactivation mediated by a GAL4-NFAT fusion protein containing the N-terminal transactivation domain of NFATp. In contrast to phorbol ester plus calcium ionophore A23187, Cot kinase increases both COX-2 promoter activity and NFAT-mediated transactivation in a cyclosporin A-independent manner. These data indicate that Cot kinase up-regulates COX-2 promoter-driven transcription through the NFAT response elements, being the Cot kinase-induced NFAT-dependent transactivation presumably implicated in this up-regulation. |
| Databáze: | OpenAIRE |
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