A5055304416- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Cellular transport and secretion
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Lipid Membrane Structure and Behavior
- Protein Degradation and Inhibitors
- Amino Acid Enzymes and Metabolism
- AI in cancer detection
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- Liver Disease Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Image Retrieval and Classification Techniques
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Radiomics and Machine Learning in Medical Imaging
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Renal cell carcinoma treatment
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- DNA Repair Mechanisms
Calithera (United States)
2013-2023
Friedrich-Alexander-Universität Erlangen-Nürnberg
2022
Health Canada
2022
Durham University
1985-2022
Royal Armouries
2022
University of Bern
2022
University of Veterinary Medicine Vienna
2022
North Carolina State University
2022
Technische Hochschule Ingolstadt
2022
Roche (Switzerland)
2022
Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization both synaptic and calcium channels to presynaptic active zone. Two 35-kilodalton proteins (p35 or syntaxins) were identified interact with vesicle protein p65 (synaptotagmin). p35 expressed only in nervous system, 84 percent identical, include carboxyl-terminal membrane anchors, concentrated on plasma at sites. An antibody...
Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports progression cirrhosis but none in the absence preexisting fibrosis on index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 1985), we identified 161 patients seen at institution and traced case notes 156. One hundred five were initially excluded as having an...
Glutamine serves as an important source of energy and building blocks for many tumor cells. The first step in glutamine utilization is its conversion to glutamate by the mitochondrial enzyme glutaminase. CB-839 a potent, selective, orally bioavailable inhibitor both splice variants glutaminase (KGA GAC). had antiproliferative activity triple-negative breast cancer (TNBC) cell line, HCC-1806, that was associated with marked decrease consumption, production, oxygen steady-state levels...
Abstract Clinical studies with bortezomib have validated the proteasome as a therapeutic target for treatment of multiple myeloma and non-Hodgkin's lymphoma. However, significant toxicities restricted intensity dosing. Here we describe antitumor activity PR-171, novel epoxyketone-based irreversible inhibitor that is currently in clinical development. In comparison to bortezomib, PR-171 exhibits equal potency but greater selectivity chymotrypsin-like proteasome. cell culture, more cytotoxic...
By three criteria, two biochemical and one immunochemical, the major postsynaptic density protein (mPSDp) is indistinguishable from 50-kilodalton (kDa) alpha subunit of a brain calmodulin-dependent kinase. First, proteins comigrate on NaDodSO4/polyacrylamide gels. Second, iodinated tryptic peptide maps are identical. Finally, monoclonal antibody (6G9) that was raised against kinase binds immunoblots to single 50 kDa band in crude homogenates both purified mPSDp fractions. The holoenzyme also...
A calcium and calmodulin-dependent protein kinase has been purified from rat brain. It was monitored during the purification by its ability to phosphorylate synaptic vesicle-associated protein, synapsin I. 300-fold sufficient produce that is 90-95% pure as determined scans of stained sodium dodecyl sulfate-polyacrylamide gels a specific activity 2.9 mumol 32P transferred per min/mg protein. Thus, relatively abundant brain enzyme, perhaps comprising much 0.3% total The Stokes radius (95 A)...
Intracellular vesicles destined to fuse with the plasma membrane and secrete their contents must have a mechanism for specifically interacting appropriate target membrane. Such is now suggested by demonstration of specific interaction between vesicular proteins proteins. The vesicle-associated (VAMPs) 1 2 bind acceptor syntaxin 1A 4 but not or 3. binding site within amino acids 194 267 1A, approximate equilibrium dissociation constant 4.7 × 10 -6 molar. These data suggest physical basis...
Bortezomib (Velcade), a dipeptide boronate 20S proteasome inhibitor and an approved treatment option for multiple myeloma, is associated with treatment-emergent, painful peripheral neuropathy (PN) in more than 30% of patients. Carfilzomib, tetrapeptide epoxyketone inhibitor, currently clinical investigation low rates PN. We sought to determine whether PN represents target-mediated adverse drug reaction (ADR).Neurodegenerative effects inhibitors were assessed vitro model utilizing...
<h3>Background</h3> Myeloid cells are an abundant leukocyte in many types of tumors and contribute to immune evasion. Expression the enzyme arginase 1 (Arg1) is a defining feature immunosuppressive myeloid leads depletion L-arginine, nutrient required for T cell natural killer (NK) proliferation. Here we use CB-1158, potent orally-bioavailable small-molecule inhibitor arginase, investigate role Arg1 regulating anti-tumor immunity. <h3>Methods</h3> CB-1158 was tested ability block...
Proteasome inhibition has been validated as a therapeutic modality in the treatment of multiple myeloma and Non-Hodgkin's lymphoma. Carfilzomib, an epoxyketone currently undergoing clinical trials malignant diseases, is highly selective inhibitor chymotrypsin-like (CT-L) activity proteasome. A chemistry effort was initiated to discover orally bioavailable analogues carfilzomib, which would have potential for improved dosing flexibility patient convenience over intravenously administered...
Botulinum neurotoxin serotype C (BoNT/C) is a 150-kDa protein produced by Clostridium botulinum, which causes animal botulism. In contrast to the other botulinum neurotoxins that contain one atom of zinc, highly purified preparations BoNT/C bind two atoms zinc per toxin molecule. zinc-endopeptidase cleaves syntaxin 1A at Lys235-Ala254 and 1B Lys252-Ala253 peptide bonds, only when they are inserted into lipid bilayer. The Lys-Ala bond present within carboxyl-terminal region not hydrolyzed....
Immunoisolation techniques have led to the purification of apical and basolateral transport vesicles that mediate delivery proteins from trans-Golgi network two plasma membrane domains MDCK cells. We showed previously these can be formed released in presence ATP mechanically perforated cells (Bennett, M. K., A. Wandinger-Ness, K. Simons, 1988. EMBO (Euro. Mol. Biol. Organ.) J. 7:4075-4085). Using virally infected cells, we monitored derived by following influenza hemagglutinin or vesicular...
Transcription from the housekeeping promoter for acetyl coenzyme A carboxylase (ACC) gene, which encodes rate-controlling enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels through novel binding sites sterol-sensitive regulatory element protein (SREBP)-1 transcription factor. The position SREBP relative those ubiquitous auxiliary factor Sp1 reminiscent that previously described sterol-regulated low density lipoprotein receptor promoter. experiments provide...
cDNA clones coding for the beta subunit of rat brain type II Ca2+/calmodulin-dependent protein kinase were isolated and sequenced. The clones, including one containing entire region, hybridize at high stringency to a single band poly(A)+ RNA length 4.8 kilobases. coded by was identified in vitro transcription followed translation resulting RNA. DNA sequence contains long open reading frame (1626 nucleotides) 542 amino acids with molecular weight 60,333, amino-terminal half which is...
Spiral computed tomography (CT) allows high-resolution examination of the pancreas, surrounding vascular structures, lymph nodes and liver. Endoscopic ultrasonography (EUS) also imaging pancreas adjacent structures but is an invasive procedure. With availability spiral CT, role EUS in investigation patients with suspected pancreatic or ampullary tumours unclear.Forty-eight clinical suspicion a tumour underwent both CT EUS. Thirty-four had surgical exploration, whom 17 resection biliary...