A5049990120- interferon and immune responses
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Cell death mechanisms and regulation
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Genetic Syndromes and Imprinting
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Immune cells in cancer
- Genetic and rare skin diseases.
- High Altitude and Hypoxia
- Inflammation biomarkers and pathways
Czech Academy of Sciences, Institute of Molecular Genetics
1997-2024
Charles University
2020-2024
University of Lausanne
2024
CRUK Lung Cancer Centre of Excellence
2014-2018
University College London
2014-2018
Czech Academy of Sciences
2000-2017
Imperial College London
2014
Ubiquitination and deubiquitination are crucial for assembly disassembly of signaling complexes. LUBAC-generated linear (M1) ubiquitin is important via various immune receptors. We show here that the deubiquitinases CYLD A20, but not OTULIN, recruited to TNFR1- NOD2-associated complexes (TNF-RSC NOD2-SC), at which they cooperate limit gene activation. Whereas recruitment depends on its interaction with LUBAC, LUBAC's M1-chain-forming capacity, A20 requires this activity. Intriguingly, exert...
Linear ubiquitination is crucial for innate and adaptive immunity. The linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP, SHARPIN, the only known ligase that generates linkages. HOIP catalytically active LUBAC component. Here, we show both constitutive Tie2-Cre-driven deletion lead to aberrant endothelial cell death, resulting in defective vascularization embryonic lethality at midgestation. Ablation tumor necrosis factor receptor 1 (TNFR1) prevents defects, death...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether to what extent signaling cells affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant FADD dependent identify TRAIL-induced secretome drive monocyte polarization myeloid-derived suppressor (MDSCs)...
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase which catalyses generation of linkages
The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion HOIP or (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic pharmacological evidence the lethal HoipE-KO Hoil-1E-KO mice caused TNFR1-induced, caspase-8-mediated apoptosis occurs independently kinase activity RIPK1. In...
The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain-interacting protein (SHARPIN), heme-oxidized IRP2 ligase-1 (HOIL-1), and HOIL-1-interacting (HOIP), is a critical regulator inflammation immunity. This highlighted by the fact that patients with perturbed ubiquitination caused mutations in Hoip or Hoil-1 genes, resulting knockouts these proteins, may simultaneously suffer from immunodeficiency autoinflammation. TLR3 plays crucial, albeit...
Thy-1 is a surface glycoprotein that attached to the plasma membrane by glycosyl-phosphatidyl-inositol anchor. Crosslinking of in rat mast cells and basophilic leukemia (RBL-2H3) induces cell activation including histamine release tyrosine phosphorylation several proteins. Here we show glycosyl-phosphatidylinositol-linked forms noncovalent complexes with src-related protein-tyrosine kinase p53/p56lyn other kinases and/or their substrates. These are resistant solubilization nonionic...
Virtual memory T cells are foreign antigen-inexperienced that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8+ in mice. Their origin, biological roles, relationship to naïve antigen-experienced incompletely understood. By analyzing T-cell receptor repertoires using retrogenic monoclonal populations, we demonstrate the virtual formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving cells. First, originate...
Abstract Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that tetra-transmembrane protein CMTM4 subunit IL-17 receptor (IL-17R). constitutively associated with IL-17R C mediate its stability, glycosylation plasma membrane localization. Both mouse human cell lines deficient in were largely unresponsive IL-17A, due their...
Formation of the immunological synapse between an antigen-presenting cell (APC) and a T leads to signal generation in both cells involved. In cells, lipid raft-associated transmembrane adaptor protein LAT plays central role. Its phosphorylation is crucial step propagation, including calcium response mitogen-activated kinase activation, largely depends on its association with SLP76 protein. Here we report discovery new palmitoylated protein, termed SCIMP. SCIMP expressed B other professional...
CD148 is a receptor-like protein-tyrosine phosphatase known to inhibit transduction of mitogenic signals in non-hematopoietic cells. Similarly, the hematopoietic lineage, inhibited signal downstream T cell receptor. However, it also augmented immunoreceptor signaling B cells and macrophages via dephosphorylating C-terminal tyrosine Src family kinases (SFK). Accordingly, endogenous compensated for loss main SFK activator CD45 murine but not Hypothetical explanations difference between other...
Article21 July 2020Open Access Source DataTransparent process Systematic analysis of the IL-17 receptor signalosome reveals a robust regulatory feedback loop Helena Draberova Laboratory Immunity & Cell Communication, BIOCEV, First Faculty Medicine, Charles University, Vestec, Czech Republic Adaptive Immunity, Institute Molecular Genetics Academy Sciences, Prague, Search for more papers by this author Sarka Janusova Daniela Knizkova Tereza Semberova Michaela Pribikova Andrea Ujevic Karel...
Bardet–Biedl syndrome (BBS) is a pleiotropic ciliopathy caused by dysfunction of primary cilia. More than half BBS patients carry mutations in one eight genes encoding for subunits protein complex, the BBSome, which mediates trafficking ciliary cargoes. In this study, we elucidated mechanisms BBSome assembly living cells and how process spatially regulated. We generated large library human cell lines deficient particular subunit expressing another tagged with fluorescent protein. analyzed...
Abstract When a BCR on mature B cell is engaged by its ligand, the becomes activated, and Ab-mediated immune response can be triggered. The initiation of signaling orchestrated kinases Src Syk families. However, proximal BCR-induced phosphorylation remains incompletely understood. According to model sequential activation kinases, acts downstream family (SFKs). In addition, independent SFKs initiated has been proposed. Both hypotheses lack sufficient evidence from relevant models, mainly...
Transmembrane adaptor proteins are membrane-anchored consisting of a short extracellular part, transmembrane domain, and cytoplasmic part with various protein-protein interaction motifs but lacking any enzymatic activity. They participate in the regulation signaling pathways by recruiting other to proximity cellular membranes where is often initiated propagated. In this work, we show that LST1/A, an incompletely characterized protein encoded MHCIII locus, palmitoylated protein. It expressed...
Tetraalkylammonium (TAA) derivatives have been reported to serve as stabilizers of asymmetrical cyanine dyes in aqueous solutions and increase the yield efficiency polymerase chain reaction (PCR) detected by end-point analysis. In this study, we compared ability various TAA (with alkyl ranging from 1 5 carbons) some other compounds enhancers real-time PCR based on fluorescence detection intercalating dye SYBR Green I (SGI). Our data indicate that chlorides potent SGI-monitored PCR. Optimal...
Abstract Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP caused NF- κ B essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as crucial component mediating the recruitment of I B-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation pro-survival response. However, recent studies have suggested gene cell death...
Glycoconjugates bearing oligosaccharide Lex, Galβ1→4(Fucα1→3)GlcNAcβ1→3R, are found on the surface of several cell types. Although recent studies have indicated that Lex both glycosphingolipids (GSL) and polylactosaminoglycans can mediate under certain experimental conditions Lex–Lex interactions, cell–cell interactions based exclusively GSLs not been demonstrated. In this study we show preincubation nonaggregating rat basophilic leukemia (RBL) cells with purified resulted in incorporation...
Transmembrane adaptor proteins (TRAPs) are important organizers and regulators of immunoreceptor-mediated signaling. A bioinformatic search revealed several potential novel TRAPs, including a highly conserved protein, proline rich 7 (PRR7), previously described as component the PSD-95/N-methyl-d-aspartate receptor protein complex in postsynaptic densities (PSD) rat neurons. Our data demonstrate that PRR7 is weakly expressed other tissues but readily up-regulated activated human peripheral...