Fiche publication
Date publication
janvier 2023
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARVET Céline
Tous les auteurs :
Griewahn L, Müller M, Peintner L, Wissler M, Weiss M, Brauns-Schubert P, Massoumi R, Borner C, Groß O, Yabal M, Charvet C, Maurer U
Lien Pubmed
Résumé
SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging the interaction of CYLD with the linear ubiquitylation assembly complex (LUBAC) component HOIP. Whether SPATA2 exhibits functions independently of CYLD is unclear. Here, we show that, while Cyld and Spata2 mice are viable, double mutants exhibit highly penetrant perinatal lethality, indicating independent functions of SPATA2 and CYLD. CyldSpata2 fibroblasts show increased M1-linked TNFR1-SC ubiquitylation and, similar to CyldSpata2 macrophages and intestinal epithelial cells, elevated pro-inflammatory gene expression compared with Cyld or Spata2 cells. We show that SPATA2 competes with OTULIN for binding to HOIP via its PUB-interacting motif (PIM) and its zinc finger domain, thereby promoting autoubiquitylation of LUBAC. Consistently, increased pro-inflammatory signaling in CyldSpata2 cells depends on the presence of OTULIN. Our data therefore indicate that SPATA2 counteracts, independently of CYLD, the deubiquitylation of LUBAC by OTULIN and thereby attenuates LUBAC activity and pro-inflammatory signaling.
Mots clés
CP: Immunology, CP: Molecular biology, CYLD, LUBAC, OTULIN, SPATA2, apoptosis, cell death, inflammation, ubiquitylation
Référence
Cell Rep. 2023 01 12;42(1):111961
