Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity
| Autor: | Samuel Tahk, Rachel R. Ogorzalek Loo, Clifford J. Bellone, Ke Shuai, Yonghui Yang, Bin Liu, Joseph A. Loo, David B. Shultz, Vasili Chernishof, Randy Yang, Sheldon Mink, Hyunduk Jang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
SUMO ligase activity
Transcription Genetic HUMDISEASE Gene Expression Inflammation Ligands General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Cell Line 03 medical and health sciences Mice 0302 clinical medicine medicine Transcriptional regulation Animals Humans STAT1 Phosphorylation RNA Small Interfering Promoter Regions Genetic 030304 developmental biology Cell Nucleus 0303 health sciences biology Biochemistry Genetics and Molecular Biology(all) Macrophages Protein Inhibitors of Activated STAT Ubiquitin ligase I-kappa B Kinase CELLIMMUNO SIGNALING 030220 oncology & carcinogenesis biology.protein Cancer research RNA Interference medicine.symptom Signal transduction Spleen |
| Zdroj: | Cell. 129(5) |
| ISSN: | 0092-8674 |
| Popis: | How inflammatory stimuli signal to the nucleus to restrict inflammation is poorly understood. Protein inhibitor of activated STAT1 (PIAS1), a transcriptional regulator that possesses small ubiquitin-related modifier (SUMO) E3 ligase activity, inhibits immune responses by selectively blocking the binding of NF-kappaB and STAT1 to gene promoters. We report here that PIAS1 becomes rapidly phosphorylated on Ser90 residue in response to various inflammatory stimuli. Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to repress transcription. Upon TNF treatment, wild-type PIAS1, but not the Ser90A mutant, becomes rapidly associated with the promoters of NF-kappaB target genes. Furthermore, IKKalpha, but not IKKbeta, interacts with PIAS1 in vivo and mediates PIAS1 Ser90 phosphorylation, a process that requires the SUMO ligase activity of PIAS1. Our results identify a signaling pathway in which proinflammatory stimuli activate the IKKalpha-mediated sumoylation-dependent phosphorylation of PIAS1 for the immediate repression of inflammatory gene activation. |
| Databáze: | OpenAIRE |
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