Protein conformational disorders, which include certain types of retinitis pigmentosa, are a set of inherited human diseases in which mutant proteins are misfolded and often aggregated. Many opsin mutants associated with retinitis pigmentosa, the most common being P23H, are misfolded and retained within the cell. Here, we describe a pharmacological ... More
Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription.
'Sp1 regulates activation of many genes implicated in tumor growth and cell cycle progression. We have previously demonstrated its implication in the up-regulation of vascular endothelial growth factor (VEGF) gene transcription following growth factor stimulation of quiescent cells, a situation where p42/p44 mitogen-activate protein kinase (MAPK) activity is dramatically increased. ... More
Phosphoinositide-specific Inositol Polyphosphate 5-Phosphatase IV Inhibits Akt/Protein Kinase B Phosphorylation and Leads to Apoptotic Cell Death.
Authors Kisseleva Marina V.; Cao Li; Majerus Philip W.;
JournalJ Biol Chem
PubMed ID11706019
'Phosphoinositide-specific inositol polyphosphate 5- phosphatase IV has the affinity for PI(3,4,5)P(3) (K(m) = 0.65 μM) that is approximately 10-fold greater than the other inositol polyphosphate 5-phosphatases, which use this substrate including SHIP, OCRL, and 5ptase II, suggesting that it may be important in controlling intracellular levels of this metabolite. We ... More
Comparison of seven different heterologous protein expression systems for the production of the serotonin transporter.
AuthorsTate CG, Haase J, Baker C, Boorsma M, Magnani F, Vallis Y, Williams DC,
JournalBiochim Biophys Acta
PubMed ID12586388
'The rat serotonin transporter (rSERT) is an N-glycosylated integral membrane protein with 12 transmembrane regions; the N-glycans improve the ability of the SERT polypeptide chain to fold into a functional transporter, but they are not required for the transmembrane transport of serotonin per se. In order to define the best ... More
Inducible expression of a dominant negative DNA polymerase-gamma depletes mitochondrial DNA and produces a rho0 phenotype.
AuthorsJazayeri M, Andreyev A, Will Y, Ward M, Anderson CM, Clevenger W,
JournalJ Biol Chem
PubMed ID12645575
'We report the inducible, stable expression of a dominant negative form of mitochondria-specific DNA polymerase-gamma to eliminate mitochondrial DNA (mtDNA) from human cells in culture. HEK293 cells were transfected with a plasmid encoding inactive DNA polymerase-gamma harboring a D1135A substitution (POLGdn). The cells rapidly lost mtDNA (t1/2 = 2-3 days) ... More
Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas.
Authors Weterman M A; van Groningen J J; Tertoolen L; van Kessel A G;
JournalProc Natl Acad Sci U S A
PubMed ID11717438
'The papillary renal cell carcinoma (RCC)-associated (X;1)(p11;q21) translocation fuses the genes PRCC and TFE3 and leads to cancer by an unknown molecular mechanism. We here demonstrate that the mitotic checkpoint protein MAD2B interacts with PRCC. The PRCCTFE3 fusion protein retains the MAD2B interaction domain, but this interaction is impaired. In ... More
Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation.
AuthorsSuzuki T, Okada Y, Semba S, Orba Y, Yamanouchi S, Endo S, Tanaka S, Fujita T, Kuroda S, Nagashima K, Sawa H,
JournalJ Biol Chem
PubMed ID15843383
'The human polyomavirus JC virus (JCV) is the causative agent of a fatal demyelinating disease, progressive multifocal leukoencephalopathy, and encodes six major proteins, including agnoprotein. Agnoprotein colocalizes with microtubules in JCV-infected cells, but its function is not fully understood. We have now identified fasciculation and elongation protein zeta 1 (FEZ1) ... More
Effect of some aldoses on growth of Saccharomyces cerevisiae inhibited with molybdenum.
AuthorsZemek J, Bílik V, Zákutná L,
JournalFolia Microbiol (Praha)
PubMed ID285
The inhibitory effect of molybdenum ions on growth of yeasts at pH 5.5 was found to be decreased by aldoses in the following order: D-talose greater than L-mannose greater than L-ribose greater than D-lyxose greater than L-galactose greater than L-arabinose greater than L-glucose greater than L-xylose. Increased concentrations of molybdenum ... More
Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage.
Authors Deverman Benjamin E; Cook Brian L; Manson Scott R; Niederhoff Robert A; Langer Ellen M; Rosová Ivana; Kulans Laura A; Fu Xiaoyun; Weinberg Justin S; Heinecke Jay W; Roth Kevin A; Weintraub Steven J;
JournalCell
PubMed ID12372300
The therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the ... More
The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
Authors van de Wetering Marc; Sancho Elena; Verweij Cornelis; de Lau Wim; Oving Irma; Hurlstone Adam; van der Horn Karin; Batlle Eduard; Coudreuse Damien; Haramis Anna Pavlina; Tjon-Pon-Fong Menno; Moerer Petra; van den Born Maaike; Soete Gwen; Pals Steven; Eilers Martin; Medema Rene; Clevers Hans;
JournalCell
PubMed ID12408868
The transactivation of TCF target genes induced by Wnt pathway mutations constitutes the primary transforming event in colorectal cancer (CRC). We show that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active in the proliferative compartment of colon ... More
Does lens intrinsic membrane protein MP19 contain a membrane-targeting signal?
AuthorsChen T, Li X, Yang Y, Erdene AG, Church RL,
JournalMol Vis
PubMed ID14735063
PURPOSE: Lens intrinsic membrane protein MP19 is the second most abundant major protein of the lens fiber cell membrane and appears to be specific to the lens. Different mutations of this protein are known to cause cataract in both humans and mice. To date, the function of MP19 in the ... More
Retention of mutant low density lipoprotein receptor in ER leads to ER stress.
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the gene encoding the low density lipoprotein receptor (LDLR). More than 50% of these mutations lead to receptor proteins that are completely or partly retained in the endoplasmic reticulum (ER). The mechanisms involved in the intracellular processing and ... More
The expression level of the voltage-dependent anion channel controls life and death of the cell.
AuthorsAbu-Hamad S, Sivan S, Shoshan-Barmatz V,
JournalProc Natl Acad Sci U S A
PubMed ID16585511
Mitochondria not only generate cellular energy, but also act as the point for cellular decisions leading to apoptosis. The voltage-dependent anion channel (VDAC), as a major mitochondrial outer-membrane transporter, has an important role in energy production by controlling metabolite traffic and is also recognized as a key protein in mitochondria-mediated ... More
Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes Requires Activator Protein-1.
AuthorsGopalan SM, Wilczynska KM, Konik BS, Bryan L, Kordula T,
JournalJ Biol Chem
PubMed ID16303762
An amyloid-associated serine proteinase inhibitor (serpin), alpha(1)-antichymotrypsin (ACT), is encoded by a gene located within the distal serpin subcluster on human chromosome 14q32.1. The expression of these distal serpin genes is determined by tissue-specific chromatin structures that allow their ubiquitous expression in hepatocytes; however, their expression is limited to a ... More
Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth.
AuthorsJung S, Mühle A, Schaefer M, Strotmann R, Schultz G, Plant TD,
JournalJ Biol Chem
PubMed ID12456670
Mammalian members of the classical transient receptor potential channel (TRPC) subfamily (TRPC1-7) are Ca(2+)-permeable cation channels involved in receptor-mediated increases in intracellular Ca(2+). Unlike most other TRP-related channels, which are inhibited by La(3+) and Gd(3+), currents through TRPC4 and TRPC5 are potentiated by La(3+). Because these differential effects of lanthanides ... More
Human TRPC5 channel activated by a multiplicity of signals in a single cell.
Here we explore the activation mechanisms of human TRPC5, a putative cationic channel that was cloned from a region of the X chromosome associated with mental retardation. No basal activity was evident but activity was induced by carbachol stimulation of muscarinic receptors independently of Ca2+ release. This is 'receptor activation', ... More
Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes. Regulation of cell cycling as a downstream molecule of thrombopoietin signaling.
AuthorsTanaka M, Kirito K, Kashii Y, Uchida M, Watanabe T, Endo H, Endoh T, Sawada K, Ozawa K, Komatsu N,
JournalJ Biol Chem
PubMed ID11278373
FKHRL1, a member of the Forkhead transcription factor family, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt. This molecule is a mammalian homolog of DAF-16, which plays an important role in the longevity of Caenorhabditis elegans. In this study we found that Akt and FKHRL1 proteins were detectable in ... More
Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB.
Authors Batlle Eduard; Henderson Jeffrey T; Beghtel Harry; van den Born Maaike M W; Sancho Elena; Huls Gerwin; Meeldijk Jan; Robertson Jennifer; van de Wetering Marc; Pawson Tony; Clevers Hans;
JournalCell
PubMed ID12408869
In the small intestine, the progeny of stem cells migrate in precise patterns. Absorptive, enteroendocrine, and goblet cells migrate toward the villus while Paneth cells occupy the bottom of the crypts. We show here that beta-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 ... More
Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.
AuthorsYu T, Robotham JL, Yoon Y,
JournalProc Natl Acad Sci U S A
PubMed ID16477035
Increased production of mitochondrial reactive oxygen species (ROS) by hyperglycemia is recognized as a major cause of the clinical complications associated with diabetes and obesity [Brownlee, M. (2001) Nature 414, 813-820]. We observed that dynamic changes in mitochondrial morphology are associated with high glucose-induced overproduction of ROS. Mitochondria undergo rapid ... More