A5048150127- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- interferon and immune responses
- NF-κB Signaling Pathways
- Cancer-related Molecular Pathways
- Invertebrate Immune Response Mechanisms
- Hippo pathway signaling and YAP/TAZ
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- Protein Kinase Regulation and GTPase Signaling
- PARP inhibition in cancer therapy
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
- Insect symbiosis and bacterial influences
- 14-3-3 protein interactions
- Aquaculture disease management and microbiota
- Cytokine Signaling Pathways and Interactions
- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Neurobiology and Insect Physiology Research
- Insect Resistance and Genetics
- Cancer Mechanisms and Therapy
- Cytomegalovirus and herpesvirus research
- Mechanisms of cancer metastasis
Breast Cancer Now
2016-2025
Institute of Cancer Research
2016-2025
Institute of Cancer Research
2023-2024
Medizinische Hochschule Hannover
2019
University of Manitoba
2018
Universidad Nacional Autónoma de México
2018
Women and Children’s Health Research Institute
2018
University of Alberta
2018
Breakthrough
2016
King's College London
2016
TNF is an inflammatory cytokine that upon binding to its receptor, TNFR1, can drive production, cell survival, or death. TNFR1 stimulation causes activation of NF-κB, p38α, and downstream effector kinase MK2, thereby promoting transcription, mRNA stabilization, translation target genes. Here we show TNF-induced MK2 results in global RIPK1 phosphorylation. directly phosphorylates at residue S321, which inhibits ability bind FADD/caspase-8 induce RIPK1-kinase-dependent apoptosis necroptosis....
The NLRP3 inflammasome responds to infection and tissue damage, rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 cell death pyroptosis. How is negatively regulated poorly understood. Here we show that activation suppressed sumoylation. sumoylated SUMO E3-ligase MAPL, stimulation-dependent desumoylation SUMO-specific proteases SENP6 SENP7 promotes activation. Defective sumoylation, either mutation acceptor lysines or depletion results in enhanced...
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic death (ICD). Although the catalytic function of RIPK1 is required to trigger death, its non-catalytic scaffold mediates strong pro-survival signaling. Accordingly, cancer cells can hijack block necroptosis evade immune detection. We generated small-molecule proteolysis-targeting chimera (PROTAC) selectively degraded human murine...
There is a growing interest in the mechanisms that control apoptosis cascade during development and adult life. To investigate regulatory events trigger whole tissues, we have devised genetically encoded caspase sensor can be detected live fixed tissue by standard confocal microscopy. The comprises two fluorophores, mRFP, monomeric red fluorescent protein (mRFP) enhanced green (eGFP), are linked an efficient specific caspase-sensitive site. Upon activation, cleaved eGFP translocates to...
The Drosophila NF-kappaB transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after gram-negative bacterial infection. a bipartite precursor protein, with N-terminal Rel homology domain and C-terminal IkappaB-like domain, similar to mammalian p100 p105. Unlike these homologs, endoproteolytically cleaved infection, allowing the module translocate nucleus. Signal-dependent activation Relish, including cleavage, requires both IkappaB kinase (IKK)...
Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, nuclear κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation directly repress TNF-induced Here, we show that regulates RIPK1's not only via activation downstream kinases NF-kB transcriptional responses, but also by repressing RIPK1 kinase activity ubiquitin-dependent inactivation. We find ubiquitin-associated...
Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death by binding to death-receptor-bound FADD. By elucidating function caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, reveal reduces DISC association activation caspase-8. Furthermore, extend our co-operative/hierarchical model caspase-8/cFLIP show does not compete with for Utilizing...
Fluorescence-activated cell sorting (FACS) is a laser-based, biophysical technology that allows simultaneous multiparametric analysis. For the analysis of dying cells, fluorescently labeled Annexin V (Annexin V(FITC)) and propidium iodide (PI) are most commonly used reagents. Instead PI, 4',6-diamidino-2-phenylindole (DAPI) can also be used. DAPI fluorescent stain binds strongly to A-T-rich regions in DNA. PI only inefficiently pass through an intact membrane and, therefore, preferentially...
Necroptosis is a lytic, inflammatory form of cell death that not only contributes to pathogen clearance but can also lead disease pathogenesis. triggered by RIPK3-mediated phosphorylation MLKL, which thought initiate MLKL oligomerisation, membrane translocation and rupture, although the precise mechanism incompletely understood. Here, we show K63-linked ubiquitin chains are attached during necroptosis ubiquitylation at K219 significantly cytotoxic potential phosphorylated MLKL. The K219R...