A5086529067- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Biotin and Related Studies
- Toxin Mechanisms and Immunotoxins
- Fungal Infections and Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related gene regulation
- Enzyme Structure and Function
- Click Chemistry and Applications
- Antifungal resistance and susceptibility
- Protein Structure and Dynamics
- Photosynthetic Processes and Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Influenza Virus Research Studies
- Mitochondrial Function and Pathology
Princess Margaret Cancer Centre
2021-2025
University Health Network
2021-2025
University of Toronto
2021-2025
Structural Genomics Consortium
2021-2024
University of British Columbia
2024
University of Guelph
2018
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of protease P (ClpP) for proteolysis. degrades damaged respiratory chain proteins necessary cancer cell survival. Despite critical role in quality control, specific degrons, or modifications that tag substrate by human ClpXP, are still unknown. We demonstrated phosphorylated serine (pSer) targets to ClpX...
The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many which govern thermotolerance, virulence, drug resistance in fungal species. However, use inhibitors as antifungal therapeutics has been precluded by human host toxicities suppression immune responses. We recently described resorcylate aminopyrazoles (RAPs) first class capable discriminating between (Cryptococcus neoformans, Candida albicans) isoforms biochemical assays. Here, we report...
Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control phosphorylation, chromatin occupancy, stability, however molecular basis remains unclear. Here we demonstrate that interacts directly with through homology Box 0 (MB0), a highly conserved region recently shown be important for activity. By NMR identified distinct peptide motif within...
Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases target proteins for proteasomal degradation. Here, we describe TPD involving the recruitment FBXO22 induce histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated NSD2 in acute lymphoblastic leukemia cells harboring gain function mutation p.E1099K, resulting growth suppression, apoptosis,...
Abstract Transmembrane Protease, Serine-2 (TMPRSS2) and TMPRSS11D are human proteases that enable SARS-CoV-2 Influenza A/B virus infections, but their biochemical mechanisms for facilitating viral cell entry remain unclear. We demonstrate these can spontaneously efficiently cleave own zymogen activation motifs, thereby activating wider protease activity on other cellular substrates. determined co-crystal structures in complexes with a native motif an engineered motif, providing insights into...
Summary Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remains an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control phosphorylation stability, however molecular basis unclear. Here we demonstrate that interacts directly with through homology Box 0 (MB0), a highly conserved region recently shown be important for activity. MB0 residues 1-148, functional unit here termed, P NUTS mino-terminal...