A5011822150- Ubiquitin and proteasome pathways
- Advanced Radiotherapy Techniques
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Sulfur Compounds in Biology
- Immunotherapy and Immune Responses
- Redox biology and oxidative stress
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Nitric Oxide and Endothelin Effects
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Potato Plant Research
- Sarcoma Diagnosis and Treatment
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- NF-κB Signaling Pathways
- Protein Degradation and Inhibitors
- Plant-Microbe Interactions and Immunity
- Animal Genetics and Reproduction
- Physiological and biochemical adaptations
- Microtubule and mitosis dynamics
- Extracellular vesicles in disease
Technion – Israel Institute of Technology
2016-2025
University of Namur
2016
Sheba Medical Center
1998-2015
Weizmann Institute of Science
2010
Wolfson Medical Center
1998-1999
Tel Aviv University
1998
Hebrew University of Jerusalem
1990-1993
Significance Whereas the role of ubiquitin system in protein degradation is well established, little known regarding regulation its own components, including catalytic arm, 26S proteasome. Here we show that stressed mammalian cells, proteasome targeted by autophagy, which requires site-specific ubiquitination receptors. The process mediated p62/SQSTM1 adapter and ubiquitin-associated domain. Independently, p62 serves also as a shuttling for ubiquitinated substrates, using PB1 This places...
Chemical synapses contain multitudes of proteins, which in common with all have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers synaptic connections typical neurons form, demand maintain protein contents these might expected place considerable metabolic demands on each neuron. Moreover, proteostasis differ according distance from global synthesis sites, availability distributed facilities, trafficking rates dynamics. To date, turnover kinetics proteins...
Background: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis atrial fibrillation (AF) has never been studied. We tested hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules induce myopathy fibrillation. Methods: collected eFat specimens from patients with (n=32) without AF (n=30) during elective heart surgery. samples were grown as organ cultures, culture medium was every 2 days. then isolated purified medium,...
Tandem mass spectrometry (MS/MS), coupled with liquid chromatography (LC), is a powerful tool for the analysis and comparison of complex protein peptide mixtures. However, extremely large amounts data that result from process are very difficult to analyze. We show how clustering similar spectra multiple LC-MS/MS runs can help in management improve The major effect spectrum reduction huge manageable size. As result, time shorter more be stored further analysis. Furthermore, quality...
The ubiquitin-proteasome pathway plays a crucial role in many cellular processes by degrading substrates tagged polyubiquitin chains, linked mostly through lysine 48 of ubiquitin. Although polymerization ubiquitin via its six other residues exists vivo as part various physiological pathways, the molecular mechanisms that determine type chains remained largely unknown. We undertook systematic, vitro, approach to evaluate E2 enzymes determining topology polyubiquitin. Because this study was...
Significance A substrate-conjugated polyubiquitin chain is accepted as the “canonical” proteasomal degradation signal. Using a cellular (human and yeast) proteomic screen in exclusive presence of nonpolymerizable ubiquitin, we show that large group proteins degraded by proteasome following monoubiquitination. The also unraveled polyubiquitin-dependent substrates, they are stabilized this ubiquitin mutant. Notably, monoubiquitination- polyubiquitination-dependent substrates display distinct...
Trichoderma virens is a biocontrol agent used in agriculture to antagonize pathogens of crop plants. In addition direct mycoparasitism soil-borne fungal pathogens, T. interacts with roots. This interaction induces systemic resistance (ISR), which reduces disease above-ground parts the plant. molecular dialog between fungus and plant leading ISR, proteins secreted by provide signals. Only few such have been characterized previously. To study secretome, were from hydroponic culture systems...
Abstract The specification and adaptability of cells rely on changes in protein composition. Nonetheless, uncovering proteome dynamics with cell-type-specific resolution remains challenging. Here we introduce a strategy for cell-specific analysis newly synthesized proteomes by combining targeted expression mutated methionyl-tRNA synthetase (MetRS) bioorthogonal or fluorescent non-canonical amino-acid-tagging techniques (BONCAT FUNCAT). Substituting leucine glycine within the MetRS-binding...
Abstract Acute exposure to acrylamide (ACR), a type-2 alkene, may lead ataxia, skeletal muscles weakness and numbness of the extremities in human laboratory animals. In present manuscript, ACR acute neurotoxicity has been characterized adult zebrafish, vertebrate model increasingly used neuropharmacology toxicology research. At behavioral level, ACR-treated animals exhibited “depression-like” phenotype comorbid with anxiety behavior. transcriptional induced down-regulation...
Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), particular. Pf, while growing inside its natural host, human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential cell remains unknown. Here we demonstrate that Pf parasites, cultured fresh donor blood, secrete within such EVs...
Abstract The gut microbiota is now well known to affect the host’s immune system. One way of bacterial communication with host cells via secretion vesicles, small membrane structures containing various cargo. Research on vesicles secreted by Gram-positive bacteria, their mechanisms interaction and immune-modulatory effects are still relatively scarce. Here we characterized size, protein content, extracellular (EVs) a newly sequenced human symbiont strain - Bifidobacterium longum AO44. We...
Abstract Cells modify their internal organization during continuous state transitions, supporting functions from cell division to differentiation. However, tools measure dynamic physiological states of individual transitioning cells are lacking. We combined live-cell imaging and machine learning monitor ERK1/2-inhibited primary murine skeletal muscle precursor cells, that transition rapidly robustly proliferating myoblasts post-mitotic myocytes then fuse, forming multinucleated myotubes. Our...
Abstract Amyloid β (Aβ) has emerged as a pathophysiological driver in age‐related macular degeneration (AMD), emphasizing its significance the aetiology of this prevalent sight‐threatening condition. The multifaceted nature AMD pathophysiology, presumably involving diverse retinal cascades, corresponds with complexity Aβ‐induced retinopathy. Therefore, targeting broad array pathogenic processes holds promise for therapeutic intervention AMD‐associated pathology. This study investigates...
Strong nanofibers composed entirely of a model globular protein, namely, bovine serum albumin (BSA), were produced by electrospinning directly from BSA solution without the use chemical cross-linkers. Control spinnability and mechanical properties was achieved manipulating protein conformation, aggregation, intra/intermolecular disulfide bonds exchange. In this manner, low-viscosity could be modified into polymer-like spinnable easily spun fibers whose as good those natural made fibrous...
Abstract Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that exposure induces food-seeking behavior, food intake, behavior intake men, but not women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB leads increased weight gain, with a sexual dimorphism towards males....
Abstract Malaria is the most serious mosquito‐borne parasitic disease, caused mainly by intracellular parasite Plasmodium falciparum . The invades human red blood cells and releases extracellular vesicles (EVs) to alter its host responses. It becomes clear that EVs are generally composed of sub‐populations. Seeking identify EV subpopulations, we subject malaria‐derived size‐separation analysis, using asymmetric flow field‐flow fractionation. Multi‐technique analysis reveals surprising...
Abstract Vesicular transport is a means of communication. While cells can communicate with each other via secretion extracellular vesicles, less known regarding organelle‐to organelle communication, particularly in the case mitochondria. Mitochondria are responsible for production energy and essential metabolic pathways cell, as well fundamental processes such apoptosis aging. Here, we show that functional mitochondria isolated from Saccharomyces cerevisiae release independent fission...
Conjugation of ubiquitin to an internal lysine is the initial step in degradation majority substrates system. For several substrates, it has been shown that first moiety conjugated N-terminal residue. In all these however, lysines also played a role modulating their stability. To better understand physiological significance this novel mode modification, was important identify proteins which completely dependent on ubiquitination. Also, although experimental evidence for ubiquitination rather...