A functional mooring sequence, known to be required for apolipoprotein B (apoB) mRNA editing, exists in the encoding neurofibromatosis type I (NF1) tumor suppressor. Editing of NF1 modifies cytidine an arginine codon ( C GA) at nucleotide 2914 a uridine U GA), creating frame translation stop codon. editing occurs normal tissue but was several-fold higher tumors. In vitro and transfection assays demonstrated that apoB RNA will take place both neural hepatoma cells. Unlike apoB, did not...

Objective— Oxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted response to oxidative promotes cardiovascular disease. Endothelial cell (EC) dysfunction an early event pathogenesis PAH. We evaluated role extracellular CypA PAH compared effects acetylated (AcK-CypA, increased by stress) on EC dysfunction. Approach Results— In transgenic mice that express high levels specifically, a phenotype was observed...

Cyclophilin A (CyPA) is a pro-inflammatory mediator involved in oxidative stress-related cardiovascular diseases. It secreted from vascular smooth muscle cell (VSMC) response to reactive oxygen species (ROS) highly regulated manner. Extracellular CyPA activates VSMCs and endothelial cells (ECs) promoting inflammation, growth, death. Recently, it was shown that acetylated (AcK-CyPA) affects its function. We investigated the role of acetylation for secretion signalling cells. used angiotensin...

Apolipoprotein B (apoB) RNA editing involves site-specific deamination of a cytidine to uridine. A mooring sequence, spacer region, and regulator region are components the apoB motif which only sequence is both necessary sufficient for editosome assembly editing. The catalytic component APOBEC-1. In rat hepatoma, stable cell lines, overexpression APOBEC-1 resulted in 3-6-fold stimulation efficiency on either endogenous or transiently expressed human RNA. these cytidines addition one at wild...

Activation-induced deaminase (AID) uses base deamination for class-switch recombination and somatic hypermutation is related to the mammalian RNA-editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 a yeast ortholog of APOBEC-1 that exhibits cytidine activity. Here, we present crystal structure at 2.0-Å resolution its use in comparative modeling AID. The models explain dimerization need trans-acting loops contribute active site formation. Substrate selectivity appears...

Recombinant mammalian proteins expressed in E. coli can be difficult to purify high yield a soluble and functional form. Various techniques have been described prevent proteolysis of and/or their sequestering as insoluble aggregates within inclusion bodies. We report conditions for expressing recombinant from that significantly enhanced the protein. demonstrate high-yield recovery native, high-molecular-weight RNA binding protein without aid fusion sequence. The principle factor increased...

We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks (1999) Biochem. J. 341, 639–645]. To examine whether similar relationship occurs vivo, hepatic was induced by feeding rats Met (L-methionine)-restricted betaine-containing diet, parameters metabolism were evaluated. There no generalized metabolic...

Angiotensin II (AngII) signal transduction in vascular smooth muscle cells (VSMC) is mediated by reactive oxygen species (ROS). Cyclophilin A (CyPA) a ubiquitously expressed cytosolic protein that possesses peptidyl-prolyl cis-trans isomerase activity, scaffold function, and significantly enhances AngII-induced ROS production VSMC. We hypothesized CyPA regulates generation promoting translocation of NADPH oxidase subunit p47phox to caveolae the plasma membrane.Overexpression CyPA-deficient...

Apolipoprotein B mRNA cytidine to uridine editing requires the assembly of a multiprotein editosome comprised minimally catalytic subunit,apolipoprotein subunit 1 (APOBEC-1), and an RNA-binding protein, APOBEC-1 complementation factor (ACF). A rat homolog has been cloned with 93.5% identity human ACF (huACF). Peptide-specific antibodies prepared against huACF immunoprecipitated protein similar mass as bound apolipoprotein (apoB) RNA in UV cross-linking reactions, thereby providing evidence...

Post-transcriptional editing of apolipoprotein B (apoB) mRNA is regulated in hepatic cells to achieve a steady state proportion edited and unedited RNA molecules. This activity catalyzed by APOBEC-1 (apoB editingcatalytic subunit 1) what has been widely accepted as nuclear event occurring during or after splicing. Introns impair the efficiency within an adjacent exon distance-dependent manner reporter RNAs. We show here that this inhibition can be overcome overexpressing enhanced on these...

Lipoprotein and apoiipoprotein parameters were studied in the male Zucker diabetic fatty (ZDF) rat at 10 20 weeks of age, corresponding to hyperinsulinemic insulinopenic type 2 diabetes mellitus, respectively.At both ages, ZDF rats had elevated serum triglycerides, free acids, corticosterone, whereas 20-week reduced thyroid hormones.At weeks, hyperlipidemia was confined elevations pre-13 triglyceride-rich (d < 1.006 g/mL) lipoproteins.By all lipoprotein density fractions increased compared...

Apolipoprotein B (apoB) mRNA editing involves site-specific deamination of cytidine to form uridine, resulting in the production an in-frame stop codon. Protein translated from edited is associated with a reduced risk atherosclerosis, and hence protein factors that regulate hepatic apoB are interest. A human essential for eight-amino acid-longer variant no known function have been recently cloned. We report both proteins, henceforth referred as ACF64 ACF65, supported APOBEC-1 (the catalytic...

Abstract In mammals, activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. SHM CSR activities require separate regions within AID. A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) at the AID C terminus is necessary for CSR, has been suggested to associate with CSR-specific cofactors. appeared late in evolution, during emergence land vertebrates from bony fish, which only display SHM. Here, we...

PLSCR1-/- mice exhibit normal, steady-state hematologic parameters but impaired emergency granulopoiesis upon in vivo administration of G-CSF. The mechanism by which PLSCR1 contributes to G-CSF-induced neutrophil production is largely unknown. We now report that the expansion bone marrow myelocytes G-CSF treatment reduced relative WT. Using SCF-ER-Hoxb8-immortalized myeloid progenitors examine progression G-CSF-driven granulocytic differentiation vitro, we found prolongs period mitotic...

Objective— Recent evidence suggests G-protein–coupled receptor-2–interacting protein-1 (GIT1) overexpression in several human metastatic tumors, including breast, lung, and prostate. Tumor metastasis is associated with an increase angiogenesis. We have showed previously that GIT1 required for postnatal angiogenesis during lung development. However, the functional role of pathological tumor growth unknown. Approach Results— In present study, we show inhibition matrigel implants as well...

Oxidative stress and inflammation play key roles in development of pulmonary arterial hypertension (PAH). We previously reported that an endothelial cell (EC)-specific cyclophilin A overexpression mouse developed many characteristics PAH. In other models cardiovascular disease, stimulates smooth muscle proliferation vascular inflammation, but mechanisms responsible for PAH have not been defined. particular, the contribution endothelial-to-mesenchymal transition A-mediated has studied....

Journal Article Multiple cooperative interactions constrain BPV-1 E2 dependent activation of transcription Get access M. Sowden, Sowden Virus Molecular Biology Group, Department BiochemistrySouth Parks Road, Oxford OX1 3QU, UK Search for other works by this author on: Academic PubMed Google Scholar S. Harrison, Harrison R. Ashfield, Ashfield A.J. Kingsman, Kingsman S.M. * To whom correspondence should be addressed Nucleic Acids Research, Volume 17, Issue 8, 25 April 1989, Pages 2959–2972,...