SFB 1054 Seminar - Klaus-Peter Knobeloch
Institut für Neuropathology, AG Molecular Genetics, University Freiburg
18.01.2018 at 12:15
Title: Ubiquitin- and ISG15-specific proteases USP8 and USP18 in adaptive and innate immunity
Protein modification by ubiquitin and ubiquitin-like proteins (UBLs) such as ISG15 or SUMO control pleiotropic biological functions and are counteracted by specific proteases (DUBs). Beside the catalytic core, most of these DUBs contain various protein-protein-interaction domains, which determine substrate specificity and recruitment to multi-molecular complexes. We identified USP8 as a novel component of the T cell receptor (TCR) signalosome that interacts with the adapter molecule Gads and the regulatory protein 14–3–3β. USP8 is critical for T cell development and function and its specific deletion of USP8 in T cells causes spontaneous inflammatory bowel disease. In contrast to USP8, USP18 is a specific isopeptidase for the UBL ISG15. ISG15 modification is strongly induced by typeI IFN and represents a classical antiviral effector system. Remarkebly, USP18 not only deconjugates ISG15 but is also a major negative regulator of the IFN response. We recently dissected enzymatic and non-enzymatic functions of USP18 in vivo. Our results suggest that inhibition of USP18 might constitute a novel antiviral strategy. Furthermore, we solved the crystal structure of USP18 and the ISG15/USP18 complex to define the molecular determinants responsible for the specificity of USP18 towards ISG15.
Venue:
BioMedical Center (BMC), Room N 01.017,
Großhaderner Str. 9, Planegg-Martinsried
Host: Vigo Heissmeyer (A03)
