SON DNA-binding protein mediates macrophage autophagy and responses to intracellular infection
| Autor: | Lester Kobzik, Sharon L. Salmon, Glen M. DeLoid, Dennis W. Metzger, David Gregory, Igor Kramnik |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cell Survival Inflammasomes Pyridines THP-1 Cells Biophysics Golgi Apparatus Biochemistry Article Cell Line Minor Histocompatibility Antigens 03 medical and health sciences Structural Biology RNA interference Interferon Gene expression Genetics medicine Autophagy Guanine Nucleotide Exchange Factors Humans RNA Small Interfering Francisella tularensis Molecular Biology 030304 developmental biology 0303 health sciences Gene knockdown biology Cell Death Intracellular parasite Gene Expression Profiling Macrophages 030302 biochemistry & molecular biology Inflammasome Cell Differentiation Cell Biology biology.organism_classification humanities Cell biology DNA-Binding Proteins Gene Expression Regulation Host-Pathogen Interactions Quinolines Tetradecanoylphorbol Acetate Interferon Regulatory Factor-3 medicine.drug Signal Transduction |
| Zdroj: | FEBS Lett |
| ISSN: | 1873-3468 |
| Popis: | Intracellular pathogens affect diverse host cellular defence and metabolic pathways. Here, we used infection with Francisella tularensis to identify SON DNA binding protein as a central determinant of macrophage activities. RNAi knockdown of SON increases survival of human macrophages following F. tularensis infection or inflammasome stimulation. SON is required for macrophage autophagy, interferon response factor 3 (IRF3) expression, type I interferon response, and inflammasome-associated readouts. SON knockdown has gene- and stimulus- specific effects on inflammatory gene expression. SON is required for accurate splicing and expression of GBF1, a key mediator of cis-Golgi structure and function. Chemical GBF1 inhibition has similar effects to SON knockdown, suggesting that SON controls macrophage functions at least in part by controlling Golgi-associated processes. |
| Databáze: | OpenAIRE |
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