A5020618698- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- RNA Research and Splicing
- interferon and immune responses
- Autophagy in Disease and Therapy
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Cell death mechanisms and regulation
- CRISPR and Genetic Engineering
- Cancer Mechanisms and Therapy
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
University of Vienna
2022-2025
Vienna Biocenter
2022-2025
Medical University of Vienna
2022-2025
Max Perutz Labs
2022-2025
Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor autophagy. We performed structure-function analysis in complex with caspase-9, HTRA2, SMAC, LC3B, which are critical autophagy proteins. Cryo–electron microscopy structures showed that forms megadalton crescent shape arcs around spacious cavity containing receptor sites...
Tristetraprolin (TTP) is a critical negative immune regulator. It binds AU-rich elements in the untranslated-regions of many mRNAs encoding pro-inflammatory mediators, thereby accelerating their decay. A key but poorly understood mechanism TTP regulation its timely proteolytic removal: degraded by proteasome through yet unidentified phosphorylation-controlled drivers. In this study, we set out to identify factors controlling stability. Cellular assays showed that strongly...
Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central this defense is the ubiquitin-proteasome system, where UBR4 acts as essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Our cryo-EM analysis of in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3 MDa ring structure, featuring central substrate-binding arena flexibly attached catalytic units....
Summary Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. BIRC6 is an exceptionally large, multidomain IAP that inhibits its targets by means atypical ubiquitin ligase activity in addition, functions as inhibitor autophagy depleting LC3B. Little known the mechanisms which interacts with fulfills these two roles. Here, we determined cryo-EM structure alone complex mitochondrial proteins, HTRA2 SMAC. We show antiparallel...
Abstract Tripartite motif 52 (TRIM52) exhibits strong positive selection in humans, yet is lost many other mammals. In contrast to what one would expect for such a non-conserved factor, TRIM52 loss compromises cell fitness. We set out determine the cellular function of TRIM52. Genetic and proteomic analyses revealed TRIM52’s involvement resolving topoisomerase 2 (TOP2)-DNA cross-links, mitigating DNA damage preventing cell-cycle arrest. Consistent with fitness-promoting function, upregulated...
Abstract Tristetraprolin (TTP) is a critical negative immune regulator. It binds AU-rich elements in the untranslated-regions of many mRNAs encoding pro-inflammatory mediators, thereby accelerating their decay. A key but poorly understood mechanism TTP regulation its timely proteolytic removal: degraded by proteasome through yet unidentified phosphorylation-controlled drivers. In this study, we set out to identify factors controlling stability. Cellular assays showed that strongly...