A5058571340- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
Linköping University
2019-2025
Abstract The deubiquitinase (DUB) ubiquitin‐specific protease 14 (USP14) is a dual domain protein that plays regulatory role in proteasomal degradation and has been identified as promising therapeutic target. USP14 comprises conserved USP ubiquitin‐like (Ubl) separated by 25‐residue linker. enzyme activity of autoinhibited solution, but enhanced when bound to the proteasome, where Ubl domains bind Rpn1 Rpt1/Rpt2 units, respectively. No structure full‐length absence proteasome yet presented,...
Abstract Ubiquitin‐specific protease 14 (USP14) is a member of the USP family responsible for catalytic removal ubiquitin (Ub) from proteins directed to proteasome, implicated in pathogenesis neurodegeneration and cancer. Crystallography cryo‐EM analysis have identified loop regions crucial deubiquitinase activity USP14, specifically those involved Ub proteasome binding. However, structural changes USP14 upon ligand binding these are minimal, indicating significant yet uncharacterized...
Abstract A large number of natural products have been advocated as anticancer agents. Many these compounds contain functional groups characterized by chemical reactivity. It is not clear whether distinct mechanisms action can be attributed to such compounds. We used a library screening approach demonstrate that substantial fraction (~20%) cytotoxic synthetic containing Michael acceptor inhibit proteasome substrate processing and induce cellular response characteristic inhibition. Biochemical...
Abstract U biquitin- s pecific p rotease 14 (USP14), is a member of the USP family responsible for catalytic removal ubiquitin (Ub) from proteins directed to proteasome, implicated in pathogenesis neurodegeneration and cancer. Crystallography cryo-EM analysis have identified loop regions crucial deubiquitinase activity USP14, specifically those involved Ub proteasome binding. However, structural changes USP14 upon ligand binding these are minimal, indicating significant yet uncharacterized...