A5058994120- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cancer-related gene regulation
- interferon and immune responses
- Invertebrate Immune Response Mechanisms
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Developmental Biology and Gene Regulation
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Inflammasome and immune disorders
- TGF-β signaling in diseases
- Wnt/β-catenin signaling in development and cancer
Technion – Israel Institute of Technology
2015-2025
Rappaport Family Institute for Research in the Medical Sciences
2000-2024
University of Würzburg
2023
Universitätsklinikum Würzburg
2023
Oncode Institute
2023
Helmholtz Zentrum München
2023
Ludwig-Maximilians-Universität München
2023
Goethe Institute
2023
Goethe University Frankfurt
2023
Weatherford College
2023
Myc proteins regulate cell growth and division are implicated in a wide range of human cancers. We show here that Fbw7, component the SCF Fbw7 ubiquitin ligase tumor suppressor, promotes proteasome-dependent c-Myc turnover vivo ubiquitination vitro . Phosphorylation on threonine-58 (T58) by glycogen synthase kinase 3 regulates binding to as well Fbw7-mediated degradation ubiquitination. T58 is most frequent site c- myc mutations lymphoma cells, our findings suggest activation one key...
The nuclear translocation of NF-kappa B follows the degradation its inhibitor, I kappa alpha, an event coupled with stimulation-dependent inhibitor phosphorylation. Prevention phosphorylation either by treating cells various reagents or mutagenesis certain putative alpha sites, abolishes inducible alpha. Yet, mechanism coupling stimulation-induced has not been resolved. Recent reports suggest a role for proteasome in degradation, but mode substrate recognition and involvement ubiquitin...
The Myc/Max/Mad transcription factor network is critically involved in cell behavior; however, there relatively little information on its genomic binding sites. We have employed the DamID method to carry out global mapping of Drosophila Myc, Max, and Mad/Mnt proteins. Each protein was tethered Escherichia coli DNA adenine-methyltransferase (Dam) permitting methylation proximal vivo sites Kc cells. Microarray analyses methylated fragments reveals multiple loci all major chromosomes. This...
Nuclear oncoproteins are among the most rapidly degraded intracellular proteins. Previous work has implicated ubiquitin-mediated proteolytic system in turnover of short-lived In present study, we have evaluated potential role ubiquitin degradation specific nuclear encoded by N-myc, c-myc, c-fos, p53 and E1A genes. Each these was synthesized vitro transcription appropriate cDNA translation resulting mRNA presence [35S]methionine. Degradation labeled proteins monitored cell-free system. ATP...
Histone deacetylases (HDACs) are thought to function as critical mediators of transcriptional repression. However, the physiological targets and posttranslational modifications class II HDACs largely unknown. Here we show that C terminus HDAC 6 is both necessary sufficient for specific association with polyubiquitin. This region contains a putative zinc finger but lacks significant similarity other known ubiquitin binding domains. Thus, have designated this PAZ domain, P olyubiquitin A...
Abstract Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes immunity, limiting tumor expansion. Mice lacking ubiquitin ligase RNF5 exhibit attenuated activation of unfolded protein response (UPR) components, which coincides with increased expression inflammasome recruitment and dendritic cells reduced antimicrobial peptides epithelial cells. Reduced UPR is also seen murine human...
The transcription factor c-Fos is a short-lived cellular protein. levels of the protein fluctuate significantly and abruptly during changing pathophysiological conditions. Thus, it clear that degradation plays an important role in its tightly regulated activity. We examined involvement ubiquitin pathway breakdown. Using mutant cell line, ts20, harbors thermolabile ubiquitin-activating enzyme, E1, we demonstrate impaired function system stabilizes vivo. In vitro, reconstituted cell-free...
In most cases, the transcriptional factor NF-κB is a heterodimer consisting of two subunits, p50 and p65, which are encoded by distinct genes Rel family. translated as precursor 105 kDa. The C-terminal domain rapidly degraded, forming mature subunit consisted N-terminal region molecule. mechanism generation not known. It has been suggested that ubiquitin-proteasome system involved in process; however, specific enzymes limited proteolysis, half molecule spared, have obscure. Palombella...
The last step in the activation of transcription factor NF-κB is signal-induced, ubiquitin- and proteasome-mediated degradation inhibitor IκBα. Although most components involved pathways have been identified, ubiquitin carrier proteins (E2) remained elusive. Here we show that two highly homologous members UBCH5 family, UBCH5b UBCH5c, CDC34/UBC3, mammalian homolog yeast Cdc34/Ubc3, are E2 enzymes process. conjugation reaction they catalyze <i>in vitro</i> specific, as do not recognize...
The ubiquitin proteolytic system plays a major role in variety of basic cellular processes. In the majority these processes, target proteins are completely degraded. one exceptional case, generation p50 subunit transcriptional regulator NF-κB, precursor protein p105 is processed limited manner: N-terminal domain yields subunit, whereas C-terminal identity mechanisms involved this unique process have remained elusive. It has been shown that Gly-rich region (GRR) at an important processing...
Members of the widely conserved Hairy/Enhancer split family basic Helix-Loop-Helix repressors are essential for proper Drosophila and vertebrate development misregulated in many cancers. While a major step forward understanding molecular mechanism(s) surrounding Hairy-mediated repression was made with identification Groucho, C-terminal binding protein (dCtBP), silent information regulator 2 (dSir2) as Hairy transcriptional cofactors, identity target genes rules governing cofactor recruitment...
Ubiquitylation regulates signaling pathways critical for cancer development and, in many cases, targets proteins degradation. Here, we report that ubiquitylation by RNF4 stabilizes otherwise short-lived oncogenic transcription factors, including β-catenin, Myc, c-Jun, and the Notch intracellular-domain (N-ICD) protein. enhances transcriptional activity of these as well Wnt- Notch-dependent gene expression. While is a SUMO-targeted ubiquitin ligase, protein stabilization requires substrate's...
Lung cancer is the most common worldwide and leading cause of cancer-related deaths in both men women. Despite development novel therapeutic interventions, 5-year survival rate for non-small cell lung (NSCLC) patients remains low, demonstrating necessity treatments. One strategy to improve translational research surrogate models reflecting somatic mutations identified as these impact treatment responses. With advent CRISPR-mediated genome editing, gene deletion well site-directed integration...
Integration of patterning cues via transcriptional networks to coordinate gene expression is critical during morphogenesis and misregulated in cancer. Using DNA adenine methyltransferase (Dam)ID chromatin profiling, we identified a protein-protein interaction between the Drosophila Myc oncogene Groucho corepressor that regulates subset direct dMyc targets. Most these shared targets affect fate or mitosis particularly neurogenesis, suggesting dMyc-Groucho complex may acquisition with mitotic...
RTK pathways establish cell fates in a wide range of developmental processes. However, how the pathway effector MAPK coordinately regulates expression multiple target genes is not fully understood. We have previously shown that EGFR causes phosphorylation and downregulation Groucho, global co-repressor widely used by many developmentally important repressors for silencing their various targets. Here, we use specific antibodies reveal dynamics Groucho MAPK, show phosphorylated response to...