A5053256748- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
- Kruppel-like factors research
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- NF-κB Signaling Pathways
- Pancreatic and Hepatic Oncology Research
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Cancer, Lipids, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Immune Cell Function and Interaction
- Cellular Mechanics and Interactions
- TGF-β signaling in diseases
- Fungal and yeast genetics research
- Liver physiology and pathology
- Nuclear Structure and Function
Hebrew University of Jerusalem
2010-2022
Weizmann Institute of Science
2013
Laboratoire de Biophotonique et Pharmacologie
2012
Centre National de la Recherche Scientifique
2012
Boston University
2005-2006
Boston Medical Center
2005
University Medical Center
2005
Tel Aviv University
2003
Only about 5% of human breast cancers can be attributed to inheritance cancer susceptibility genes, while the balance are considered sporadic in origin. Breast incidence varies with diet and other environmental influences, including carcinogen exposure. However, effects carcinogens on cell growth control pathways poorly understood. Here we have examined oncogenic signaling that activated mammary tumors mice treated prototypical polycyclic aromatic hydrocarbon (PAH) 7,12-dimethylbenz[...
The complex host-pathogen interplay involves the recognition of pathogen by host's innate immune system and countermeasures taken pathogen. Detection invading bacteria host leads to rapid activation transcription factor NF-κB, followed inflammation eradication intruders. In response, some pathogens, including enteropathogenic Escherichia coli (EPEC), acquired means blocking NF-κB activation. We show that inhibition EPEC injection NleE into cell. Importantly, we inhibits preventing IKKβ...
Abstract Recent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. β-catenin is a critical coactivator this signaling and regulated complex fashion by phosphorylation, degradation, nuclear translocation. Glycogen synthase kinase 3β (GSK3β) phosphorylation NH2-terminal domain targets it for ubiquitination proteosomal degradation. We hypothesized that expression kinase-inactive GSK3β (KI-GSK3β) mammary glands would function...
Guided cell migration is a key mechanism for positioning in morphogenesis. The current model suggests that the spatially controlled activation of receptor tyrosine kinases (RTKs) by guidance cues would limit Rac activity at leading edge, which critical establishing and maintaining polarized protrusions front. However, little known about mechanisms RTKs control local Rac. Here, using multidisciplinary approach, we identify GTP exchange factor (GEF) vav as regulator downstream developmentally...
Changes in gene expression represent a major mechanism by which cells respond to stress. We and other investigators have previously shown that the yeast RNA polymerase II subunit Rpb4p is required for transcription under various stress conditions, but not optimal growth conditions. Here we show that, addition its role transcription, also mRNA export, only when are exposed The roles of export can be uncoupled genetically specific mutations Rpb4p. Both functions maintain cell viability during...
Mammalian DNA replication is a highly organized and regulated process. Large, Mb-sized regions are replicated at defined times along S-phase. Replication Timing (RT) thought to play role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic RT profiles. However, only germline mutations passed offspring affect genomic composition. Therefore, germ cell information necessary evaluate influences of genome. We adapted mapping technique for limited...
Vav1 functions as a signal transducer protein in the hematopoietic system, where it is exclusively expressed. was recently implicated several human cancers, including lung, pancreatic and neuroblasoma. In this study, we analyzed expression function of breast tumors cancer cell lines. Immunohistochemical analysis primary carcinomas indicated that expressed 62% 65 tested correlated positively with estrogen receptor expression. Based on published gene profiling 50 lines, Vav1-expressing lines...
The guanine nucleotide exchange factor (GEF) Vav1 is an essential signal transducer protein in the hematopoietic system, where it expressed physiologically. It also involved several human malignancies. Tyrosine phosphorylation at amino terminus plays a central role regulating its activity; however, of carboxyl terminal tyrosine residues unknown. We found that mutation either Tyr-826 (Y826F) or Tyr-841 (Y841F) to phenylalanine led loss GEF activity. When these mutants were ectopically...
// Shulamit Sebban 1,* , Marganit Farago Shiran Rabinovich 1 Galit Lazer Yulia Idelchuck Lena Ilan Eli Pikarsky 2 and Katzav Departement of Developmental Biology Cancer Research, Institute for Medical Research Israel-Canada, Hadassah School - Hebrew University, Jerusalem, Israel Department Immunology & Pathology, * These authors contributed equally to this work Correspondence: Katzav, email: Keywords : Vav1, CSF1, Lung Cancer, Growth Factors Received June 16, 2014 Accepted August 26,...
MINT‐7302186: XBP1‐u (uniprotkb:P17861‐1) binds (MI:0407) to Proteasome subunit alpha 6 (uniprotkb:P60900) by pull down (MI:0096)
Abstract Vav1 is physiologically active as a GDP/GTP nucleotide exchange factor (GEF) in the hematopoietic system. Overexpression of multiple tumor types known to enhance oncogenicity, yet whether or not bona fide oncogene still matter debate. Although mutations were recently identified human cancers various origins, functional activities these mutants are known. We tested transforming potential three lung adenocarcinoma: E59K, D517E, and L801P. Results from several assays indicative such...
To explore the contribution of Vav1, a hematopoietic signal transducer, to pancreatic ductal adenocarcinoma (PDAC) development, we generated transgenic mouse lines expressing, K-Ras G12D , or both and Vav1 in acinar cells. Co-expression synergistically enhanced acinar-to-ductal metaplasia (ADM) formation, far exceeding number lesions developed mice. Mice expressing only did not develop ADM. Moreover, incidence PDAC /Vav1 was significantly higher than Discontinuing expression mice elicited...
Abstract Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of each allele different, and identity early varies between cells. By taking advantage stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped genome-wide AS-RT loci, independently genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression include new gene families involved specifying identity. combining...
Histone acetylation levels are reduced during mitosis. To study the mitotic regulation of H3K9ac, we used an array inhibitors targeting specific histone deacetylases. We evaluated involvement targeted enzymes in regulating H3K9ac all stages by immunofluorescence and immunoblots. identified HDAC2, HDAC3, SIRT1 as modulators levels. HDAC2 inhibition increased prophase, whereas HDAC3 or metaphase. Next, performed ChIP-seq on mitotic-arrested cells following these found that both have a similar...
Interferon Stimulated Gene 12a, ISG12a, is a member of family small intracellular non-secreted proteins (10–20 kDa), mainly induced by type I IFNs and slightly II IFN. It has been shown that full length ISG12 (ISG12a) overexpressed in breast cancer, yet the biological function largely unknown. Here we show transient transfection ISG12a into various mammalian cell lines leads to accumulation cells initially G1 phase cycle, followed sub phase, transfected with undergo morphological changes,...
Vav1 is normally and exclusively expressed in the hematopoietic system where it functions as a specific GDP/GTP nucleotide exchange factor (GEF), firmly regulated by tyrosine phosphorylation. Mutations overexpression of malignancies, human cancers various histologic origins, are well documented. To reveal whether different tissues suffices for promoting development malignant lesions, we transgenic mice using ubiquitous ROSA26 promoter (Rosa Vav1). We detected expression epithelial organs...
Abstract Histone acetylation levels are reduced during mitosis. To study the mitotic regulation of H3K9ac we used an array inhibitors targeting specific histone deacetylases. We evaluated involvement targeted enzymes in regulating all stages by immunofluorescence and immunoblots. identified HDAC2, HDAC3 SIRT1 as modulators levels. HDAC2 inhibition increased prophase, whereas or metaphase. Next, performed ChIP-seq on mitotic-arrested cells following these found that both have a similar impact...