A5078500627- Cellular Mechanics and Interactions
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Click Chemistry and Applications
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- Chemical Synthesis and Analysis
- Spaceflight effects on biology
- DNA Repair Mechanisms
- Force Microscopy Techniques and Applications
- Pharmacogenetics and Drug Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Skin and Cellular Biology Research
- Neuroblastoma Research and Treatments
- MicroRNA in disease regulation
- Microbial Natural Products and Biosynthesis
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
Merck & Co., Inc., Rahway, NJ, USA (United States)
1990-2020
University of Utah
1999
Columbia University
1995
Albert Einstein College of Medicine
1990-1991
The MYC oncogene is upregulated in human cancers by translocation, amplification, and mutation of cellular pathways that regulate Myc. Myc/Max heterodimers bind to E box sequences the promoter regions genes activate transcription. inhibitor Omomyc can reduce ability specific promoters target binding directly as demonstrated chromatin immunoprecipitation (CHIP). Here, we demonstrate both a proximity ligation assay (PLA) double (ReCHIP) preferentially binds Max, not Myc, mediate inhibition...
A monomeric actin bundling protein with a native molecular weight of approximately 50,000 (ABP-50) has been isolated from amoebae Dictyostelium discoideum. ABP-50 cross-links F-actin to form tightly packed bundles, some which are highly ordered. It exhibits Kd 2.1 microM and molar ratio 1:1 in bundles. Calcium ATP at physiological concentrations have no effect on these activities. is immunologically unrelated 30-kDa protein, previously described Dictyostelium. Immunofluorescence...
Abstract In this work we evaluate the cartical expansion model for amoeboid chemo‐taxis with regard to new information about molecular events in cytoskeleton following chemo‐tactic stimulation of Dictyostelium amoebae. A rapid upshift concentration chemoattrac‐tant can be used synchronize motile behavior a large population cells. This synchrony presents an opportunity study biochemical basis morphological changes such as pseudopod extension that are required chemotaxis. Changes composition...
Abstract ABP‐50 is the elongation factor‐1 alpha (EF‐1 alpha) of Dictyostelium discoideum (Yang et al.: Nature 347:494–496, 1990). also an actin filament binding and bundling protein (Demma J. Biol. Chem . 265:2286–2291, In present study we have investigated compartmentalization in both resting stimulated cells. Immunofluorescence microscopy shows that addition to being colocalized with F‐actin surface extensions unstimulated cells, exhibits a diffuse distribution throughout cytosol. Upon...
Myc, a transcription factor with oncogenic activity, is upregulated by amplification, translocation, and mutation of the cellular pathways that regulate its stability. Inhibition Myc oncogene various modalities has had limited success. One inhibitor, Omomyc, in vivo activity. Here, we report mini‐protein, referred to as Mad, which derived from antagonist Mxd1. Mad localizes nucleus cells 10‐fold more potent than Omomyc inhibiting Myc‐driven cell proliferation. Similar Mxd1, also interacts...
The Myc transcription factor represents an "undruggable" target of high biological interest due to its central role in various cancers. An abbreviated form the c-Myc protein, called Omomyc, consists DNA-binding domain and a coiled-coil region facilitate dimerization 90 amino acid polypeptide. Here we present our results evaluate synthesis Omomyc using three complementary strategies: linear Fmoc solid-phase peptide (SPPS) several advancements for difficult sequences, native chemical ligation...
Farnesyl protein transferase (FPT) is an alpha/beta heterodimeric zinc enzyme that catalyzes posttranslational farnesylation of many key cellular regulatory proteins, including oncogenic Ras. On the basis recently reported crystal structure FPT complexed with a CVIM peptide and alpha-hydroxyfarnesylphosphonic acid, site-directed mutagenesis active site was performed so residues are responsible for substrate binding catalysis could be identified. Eight single mutants, K164N alpha, Y166F Y166A...
Protein farnesyltransferase (FPT) is a 97 000 Da heterodimeric enzyme that catalyzes post-translational farnesylation of many cellular regulatory proteins including p21 Ras. To facilitate the construction site-directed mutants, novel translationally coupled, two-cistron Escherichia coli expression system for rat FPT has been developed. This enabled yields >5 mg purified protein per liter E.coli culture to be obtained. The E.coli-derived demonstrated an activity comparable isolated from other...
Exosomes are microvesicles secreted by body cells for intercellular communication. The circular RNA circ_0000338 was found to be present in extracellular vesicles and improve the chemoresistance of colorectal cancer (CRC) cells. However, role exosomal 5-fluorouracil (5-FU) resistance CRC is largely unknown. levels circ_0000338, microRNA 217 (miR-217), miR-485-3p were detected using quantitative real-time PCR (qRT-PCR). 50% inhibitory concentration (IC50) values 5-FU, cell proliferation,...