Inflammasome Activated Caspase 7 Cleaves ARTD1 to Enhance the Expression of a Subset of NF-kappaB Target Genes in Macrophages
Event details
| Date | 25.01.2012 |
| Hour | 11:00 |
| Speaker | Dr. Michael HOTTIGER University of Zurich-Irchel - Institute of Veterinary Biochemistry & Molecular Biology - Zürich |
| Location | |
| Category | Conferences - Seminars |
Caspase 1 is part of the inflammasome, which is assembled upon pathogen recognition, while caspases 3 and/or 7 are mediators of apoptotic and non-apoptotic functions. ADP-ribosyltransferase Diphtheria toxin-like 1(ARTD1, formerly called poly-ADP-ribose polymerase 1 (PARP1)) cleavage is a hallmark of apoptosis yet not essential, suggesting it has another physiological role. Here we show that after LPS stimulation, caspase 7 is activated by caspase 1, tanslocates to the nucleus and cleaves ARTD1 at the promoters of a subset of negatively regulated NF-kappaB target genes. Mutating the ARTD1 cleavage site D214 renders ARTD1 uncleavable and inhibits ARTD1 release from chromatin and chromatin decondensation, thereby restraining the expression of cleavage-dependent NF-kappaB target genes. These findings propose an apoptosis-independent regulatory role for caspase 7-mediated ARTD1 cleavage in pro-inflammatory gene expression and provide novel insight into inflammasome signaling.
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