RT Journal Article
SR Electronic
T1 XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900346
DO 10.26508/lsa.201900346
VO 2
IS 4
A1 Ellwanger, Kornelia
A1 Briese, Selina
A1 Arnold, Christine
A1 Kienes, Ioannis
A1 Heim, Valentin
A1 Nachbur, Ueli
A1 Kufer, Thomas A
YR 2019
UL http://www.life-science-alliance.org/content/2/4/e201900346.abstract
AB 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-κB 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.