A5026512599- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Melanoma and MAPK Pathways
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Cell death mechanisms and regulation
- Cytokine Signaling Pathways and Interactions
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
Cedars-Sinai Medical Center
2024-2025
Sanford Burnham Prebys Medical Discovery Institute
2015-2024
Discovery Institute
2015-2024
High Throughput Biology (United States)
2023
National Cancer Institute
1997-2020
Technion – Israel Institute of Technology
2004-2020
Tsinghua University
2019
Institute for Medical Research
2006-2015
The University of Melbourne
2012
Peter MacCallum Cancer Centre
2012
The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. rapid activation by ionizing radiation radiomimetic agents largely dependent on the ATM kinase. phosphorylated shortly damage, resulting in enhanced stability activity p53. Mdm2 oncoprotein pivotal negative In response drugs, undergoes ATM-dependent phosphorylation prior accumulation. This results decrease its reactivity with 2A10 monoclonal antibody....
Activation of the tumor suppressor p53 by stress and damage stimuli often correlates with induction kinases, Jun-NH 2 kinase (JNK). As JNK association plays an important role in stability, present study we have elucidated relationship between JNK-signaling pathway stability activity. Expression a constitutively active form JNKK upstream kinase, mitogen-activated protein (ΔMEKK1), increased level exogenously transfected null (10.1) cells as well endogenous MCF7 breast cancer cells. Increased...
Mutations in PARKIN, pten-induced putative kinase 1 (PINK1), and DJ-1 are individually linked to autosomal recessive early-onset familial forms of Parkinson disease (PD). Although mutations these genes lead the same state, functional relationships between them how their respective disease-associated cause PD largely unknown. Here, we show that Parkin, PINK1, formed a complex (termed PPD complex) promote ubiquitination degradation Parkin substrates, including itself Synphilin-1 neuroblastoma...
Metabolic rewiring is an established hallmark of cancer, but the details this at a systems level are not well characterized. Here we acquire insight in melanoma cell line panel by tracking metabolic flux using isotopically labeled nutrients. profiling and balance analysis were used to compare normal melanocytes lines both normoxic hypoxic conditions. All cells exhibited Warburg phenomenon; they more glucose produced lactate than melanocytes. Other changes observed that described phenomenon....
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, drug However, how MITF suppressed in vivo...
PRMT5 expression in melanoma suppresses inflammation and antigen presentation, suggesting that its inhibition could potentiate immunotherapy.
Growing evidence supports the importance of gut microbiota in control tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa promote anti-tumor immunity. Addition inulin or mucin diet C57BL/6 mice induces immune responses inhibition BRAF mutant melanoma a subcutaneously implanted syngeneic mouse model. Mucin fails inhibit germ-free mice, indicating is required for activation response. Inulin drive distinct changes microbiota, as inulin, but not mucin,...
Abstract Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD) molecules that induce by the ubiquitin-proteasome system (UPS) offer new opportunities to engage targets remain challenging be inhibited conventional small molecules. One fundamental element in process is E3 ligase. However, less than 2% amongst hundreds of ligases human genome have been engaged current studies TPD field, calling for recruiting additional ones further enhance therapeutic potential...
In higher eukaryotes, reactive oxygen species (ROS) are generated during respiration in mitochondria the course of reduction molecular as well by distinct enzyme systems. ROS have been implicated regulation diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. The reduction-oxidation (redox) state cell is primarily a consequence precise balance between levels endogenous thiol buffers present cell,...
In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount p53–JNK complex was inversely correlated with level. A peptide corresponding to binding site on efficiently blocked ubiquitination p53. Similarly, lacking exhibits a longer half-life than wt . Outcompeting association increased level p53, whereas overexpression phosphorylation mutant form inhibited accumulation. JNK–p53 and Mdm2–p53 complexes were preferentially found G 0 /G 1 S/G 2 M phases cell...
c-Jun N-terminal kinase (JNK)-mediated cell signaling pathways are regulated endogenously in part by protein-protein interactions with glutathione S-transferase P1–1 (GSTP1–1) (1Adler V. Yin Z. Fuchs S.Y. Benezra M. Rosario L. Tew K.D. Pincus M.R. Sardana Henderson C.J. Wolf C.R. Davis R.J. Ronai EMBO J. 1999; 18: 1321-1334Crossref PubMed Scopus (948) Google Scholar). Using purified recombinant proteins, combined fluorescence resonance energy transfer technology, we have found that the C...