'Lipid phosphate monoesters including phosphatidic acid, lysophosphatidic acid, sphingosine 1-phosphate and ceramide 1-phosphate are intermediates in phosho- and sphingo-lipid biosynthesis and also play important roles in intra- and extra-cellular signaling. Dephosphorylation of these lipids terminates their signaling actions and, in some cases, generates products with additional biological activities or metabolic ... More
Discovery of acetyl-coenzyme A carboxylase 2 inhibitors: comparison of a fluorescence intensity-based phosphate assay and a fluorescence polarization-based ADP Assay for high-throughput screening.
AuthorsLiu Y, Zalameda L, Kim KW, Wang M, McCarter JD,
JournalAssay Drug Dev Technol
PubMed ID17477831
'Acetyl-coenzyme A carboxylase (ACC) enzymes exist as two isoforms, ACC1 and ACC2, which play critical roles in fatty acid biosynthesis and oxidation. Though each isoform differs in tissue and subcellular localization, both catalyze the biotin- and ATP-dependent carboxylation of acetyl-coenzyme A to generate malonyl-coenzyme A, a key metabolite in the ... More
High-throughput screening for Hsp90 ATPase inhibitors.
AuthorsAvila C, Hadden MK, Ma Z, Kornilayev BA, Ye QZ, Blagg BS,
JournalBioorg Med Chem Lett
PubMed ID16530412
Recently, we reported a useful assay for the determination of yeast Hsp90 ATPase activity. Using this assay, high-throughput screening of approximately 10,000 compounds was performed to determine the feasibility of this assay on large scale. Results from high-throughput screening indicated that the assay was reproducible (av Z-factor = 0.80) and ... More
Development and optimization of a useful assay for determining Hsp90's inherent ATPase activity.
AuthorsAvila C, Kornilayev BA, Blagg BS,
JournalBioorg Med Chem
PubMed ID16213144
The Hsp90 molecular chaperone is responsible for the conformational maturation of nascent polypeptides and the rematuration of denatured proteins. Inhibition of Hsp90 represents a promising approach towards the treatment of cancer because numerous signaling cascades can be simultaneously targeted by disruption of the Hsp90-mediated process. Hsp90's ATPase activity is essential ... More
Fly and mammalian lipid phosphate phosphatase isoforms differ in activity both in vitro and in vivo.
AuthorsBurnett C, Howard K
JournalEMBO Rep
PubMed ID12856002
Wunen (Wun), a homologue of a lipid phosphate phosphatase (LPP), has a crucial function in the migration and survival of primordial germ cells (PGCs) during Drosophila embryogenesis. Past work has indicated that the LPP isoforms may show functional redundancy in certain systems, and that they have broad-range lipid phosphatase activities ... More
Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells.
AuthorsLuquain C, Singh A, Wang L, Natarajan V, Morris AJ
JournalJ Lipid Res
PubMed ID12837850
Lysophosphatidic acid (LPA) is a receptor-active lipid mediator with a broad range of biological effects. Ovarian cancer cells synthesize LPA, which promotes their motility, growth, and survival. We show that a murine homolog of a human protein previously reported to hydrolyze LPA is a highly selective detergent-stimulated LPA phosphatase that ... More
XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators.
AuthorsLuz JG, Hassig CA, Pickle C, Godzik A, Meyer BJ, Wilson IA
JournalGenes Dev
PubMed ID12672694
In Caenorhabditis elegans, an X chromosome-counting mechanism specifies sexual fate. Specific genes termed X-signal elements, which are present on the X chromosome, act in a concerted dose-dependent fashion to regulate levels of the developmental switch gene xol-1. In turn, xol-1 levels determine sexual fate and the activation state of the ... More
Kinetic analysis of tubulin assembly in the presence of the microtubule-associated protein TOGp.
AuthorsBonfils C, Bec N, Lacroix B, Harricane MC, Larroque C
JournalJ Biol Chem
PubMed ID17178729
The microtubule-associated protein TOGp, which belongs to a widely distributed protein family from yeasts to humans, is highly expressed in human tumors and brain tissue. From purified components we have determined the effect of TOGp on thermally induced tubulin association in vitro in the presence of 1 mm GTP and ... More
A functionally active human F1F0 ATPase can be purified by immunocapture from heart tissue and fibroblast cell lines. Subunit structure and activity studies.
Human mitochondrial F(1)F(0) ATP synthase was isolated with a one-step immunological approach, using a monoclonal antibody against F(1) in a 96-well microplate activity assay system, to establish a method for fast high throughput screening of inhibitors, toxins, and drugs with very small amounts of enzyme. For preparative purification, mitochondria from ... More
Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.
Authors
JournalCell Rep
PubMed ID30699359
New insights into the role of conserved, essential residues in the GTP binding/GTP hydrolytic cycle of large G proteins.
Authors
JournalJ Biol Chem
PubMed ID16469737
The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma.
Authors
JournalMol Cell
PubMed ID33571422
The antidepressant sertraline targets intracellular vesiculogenic membranes in yeast.
Authors
JournalGenetics
PubMed ID20457874
Phosphate Assay Kit in One Cell for Electrochemical Detection of Intracellular Phosphate Ions at Single Cells.
Authors
JournalFront Chem
PubMed ID31179270
Hsp90 N- and C-terminal double inhibition synergistically suppresses Bcr-Abl-positive human leukemia cells.
Authors
JournalOncotarget
PubMed ID28036294
Co-chaperones TIMP2 and AHA1 Competitively Regulate Extracellular HSP90:Client MMP2 Activity and Matrix Proteolysis.
Authors
JournalCell Rep
PubMed ID31412254
Wound-induced Ca2+ wave propagates through a simple release and diffusion mechanism.