A5021913429- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Microtubule and mitosis dynamics
- Vascular Malformations Diagnosis and Treatment
- Sperm and Testicular Function
- Meningioma and schwannoma management
- Renal and related cancers
- Histiocytic Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Cancer Research and Treatments
- biodegradable polymer synthesis and properties
- Diet and metabolism studies
Technion – Israel Institute of Technology
2013-2025
Rambam Health Care Campus
2023-2024
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...
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...
Significance Multistep reactions, such as degradation of proteins by the ubiquitin–proteasome system, require that different components will be colocalized to an assembly allows catalysis all steps in efficient and processive manner. In absence colocalization, floating individual around cell would slow cascade reactions. We demonstrated assemblies are generated nucleus both under basal stressed conditions play a role nuclear proteins, unassembled subunits proteasome, unfolded suggesting they...
Abstract Acute myeloid leukemia (AML) remains incurable, largely due to its resistance conventional treatments. Here, we find that increased abundance of the ubiquitin ligase RNF5 contributes AML development and survival. High expression in patient specimens correlates with poor prognosis. inhibition decreases cell growth culture, patient-derived xenograft (PDX) samples vivo, delays MLL-AF9–driven leukemogenesis mice, prolonging their causes transcriptional changes overlap those seen upon...
Multiple myeloma (MM) poses a significant therapeutic challenge due to its persistent progression and low survival rate. Although the proteasome inhibitor bortezomib has revolutionized MM treatment, aggressiveness drug resistance remain critical concerns. To tackle this problem, we developed AMD3100-targeted Bortezomib Liposomes (ATBL) designed for targeted delivery of cells. Uptake ATBL into cells was dependent on CXCR4 enhanced compared nontargeted liposomes, both in vitro vivo. Treating...
By establishing multi-omics pipelines, we uncover overexpression and gene copy-number alterations of nucleoporin-93 (NUP93), a nuclear pore component, in aggressive human mammary tumors. NUP93 enhances transendothelial migration matrix invasion vitro, along with tumor growth metastasis animal models. These findings are supported by analyses two sets naturally occurring mutations: rare oncogenic mutations inactivating familial nephrotic syndrome mutations. Mechanistically, binds importins,...
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many these can carry out non-canonical functions. They were shown to be involved important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis. In work, we provide evidence tryptophanyl-tRNA might negative...
Ubiquitin (Ub) is a small protein (8 kDa) found in all eukaryotic cells, which conjugated covalently to numerous proteins, tagging them for recognition by downstream effector. One of the best characterized functions Ub targeting proteins either selective degradation proteasome, or bulk autophagy-lysosome system. The executing arm UPS 26S large multicatalytic complex. While much known about synthesis and assembly proteasome's subunits, mechanism(s) underlying its removal has remained obscure,...
Cyclic peptides containing unnatural amino acids can modulate Lys-48 ubiquitin chains in cells and animals.
Messenger RNA display of peptides containing non-proteinogenic amino acids, referred to as RaPID system, has become one the leading methods express libraries consisting more than trillion-members macrocyclic peptides, which allows for discovering de novo bioactive ligands. Ideal should have dissociation constants (KD ) low single-digit values in nanomolar range towards a specific target interest. Here, twofold strategy discover optimized within this affinity regime is described. First,...
Abstract Mechanisms regulating nuclear organization control fundamental cellular processes, including the cell and chromatin organization. Their disorganization, aberrant architecture, has been often implicated in transformation. Here, we identify Lamin A, among proteins essential for as SPANX (sperm protein associated with nucleus on X chromosome), a cancer testis antigen previously linked to invasive tumor phenotypes, interacting melanoma. interaction A was mapped immunoglobulin fold-like...
The ubiquitin–proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due constant mechanical and metabolic stress, UPS has a key role in cardiac physiology pathophysiology. While altered proteasomal activity contributes variety pathologies, such heart failure ischemia/reperfusion injury (IRI),...
An important area of modern biology consists understanding the relationship between genotype and phenotype. However, to understand this it is essential investigate one principal links them: proteome. With development recent mass-spectrometry approaches, now possible quantify entire proteomes thus relate them different phenotypes. Here, we present a comparison proteome two extreme developmental states in well-established model organism Drosophila melanogaster: adult embryo. Protein modules...