XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures
- Author(s)
- Ellwanger, K; Briese, S; Arnold, C; Kienes, I; Heim, V; Nachbur, U; Kufer, TA;
- Details
- Publication Year 2019-08,Volume 2,Issue #4,Page e201900346
- Journal Title
- Life Science Alliance
- Publication Type
- Journal Article
- Abstract
- The receptor interacting serine/threonine kinase 2 (RIPK2) is essential for linking activation of the pattern recognition receptors NOD1 and NOD2 to cellular signaling events. Recently, it was shown that RIPK2 can form higher order molecular structures in vitro. Here, we demonstrate that RIPK2 forms detergent insoluble complexes in the cytosol of host cells upon infection with invasive enteropathogenic bacteria. Formation of these structures occurred after NF-kappaB activation and depended on the caspase activation and recruitment domain of NOD1 or NOD2. Complex formation upon activation required RIPK2 autophosphorylation at Y474 and was influenced by phosphorylation at S176. We found that the E3 ligase X-linked inhibitor of apoptosis (XIAP) counteracts complex formation of RIPK2, accordingly mutation of the XIAP ubiquitylation sites in RIPK2 enhanced complex formation. Taken together, our work reveals novel roles of XIAP in the regulation of RIPK2 and expands our knowledge on the function of RIPK2 posttranslational modifications in NOD1/2 signaling.
- Publisher
- Life Science Alliance
- Research Division(s)
- Inflammation
- PubMed ID
- 31350258
- Publisher's Version
- https://doi.org/10.26508/lsa.201900346
- Open Access at Publisher's Site
https://doi.org/10.26508/lsa.201900346- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-08-13 12:35:12
Last Modified: 2019-08-13 01:06:54