title: SPATA2: more than a missing link.
abstract: The assembly of the TNFR1 signalling complex (TNF-RSC) depends on K63- and M1-linked ubiquitylation, promoting the recruitment of complex constituents and the stability of the complex. Ubiquitylation is a dynamic process, controlled by E3 ubiquitin ligases as well as deubiquitinases, such as CYLD and OTULIN. A novel molecule, SPATA2, which is crucial for recruiting and activating the deubiquitinase CYLD within the TNF-RSC, has now been identified by four different studies. Loss of SPATA2 was shown to result in increased TNF-, but also NOD2-mediated proinflammatory signalling. Importantly, SPATA2 is instrumental for TNF-induced cell death, and a closer look at these findings suggests that SPATA2 possibly has functions beyond promoting the activity of CYLD.
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan Meier Strasse 17, Freiburg 79104, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University of Freiburg, Albertstrasse 19a, Freiburg 79104, Germany.|BIOSS, Centre for Biological Signaling Studies, Hebelstrasse 2, Freiburg 79104, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schlicher
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan Meier Strasse 17, Freiburg 79104, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University of Freiburg, Albertstrasse 19a, Freiburg 79104, Germany.|BIOSS, Centre for Biological Signaling Studies, Hebelstrasse 2, Freiburg 79104, Germany.
authors.forename: Prisca
authors.initials: P
authors.lastname: Brauns-Schubert
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan Meier Strasse 17, Freiburg 79104, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University of Freiburg, Albertstrasse 19a, Freiburg 79104, Germany.|BIOSS, Centre for Biological Signaling Studies, Hebelstrasse 2, Freiburg 79104, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schubert
authors.affiliation: Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan Meier Strasse 17, Freiburg 79104, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University of Freiburg, Albertstrasse 19a, Freiburg 79104, Germany.|BIOSS, Centre for Biological Signaling Studies, Hebelstrasse 2, Freiburg 79104, Germany.
authors.forename: Ulrich
authors.identifier: 0000-0002-2504-1517
authors.initials: U
authors.lastname: Maurer
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D011506:Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I