Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients.
|Abstract||Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients r ... [truncated at 450 characters in length]|
|Author||Petrie, Kirsten A; Lee, Wen Hwa; Bullock, Alex N; et al|
|Subject||Activin Receptors, Type I Adolescent Enzyme Activation Female Humans Middle Aged Mutation, Missense Myositis Ossificans Phenotype Point Mutation Protein Kinases genetics genetics|
Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.
|Abstract||Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in ... [truncated at 450 characters in length]|
|Author||Brocker, Chad; Lassen, Natalie; Estey, Tia; et al|
|Subject||Aldehyde Dehydrogenase Aldehydes Animals CHO Cells Cricetinae Cricetulus Crystallography, X-Ray Female Gene Expression Regulation, Enzymologic Humans Male Mice Osmosis Proteins Tissue Distribution metabolism physiology chemistry methods metabolism physiology|
Quinone oxidoreductase-2-mediated prodrug cancer therapy.
|Abstract||DNA-damaging agents are widely used in cancer treatment despite their lack of tumor specificity. Human NQO2 (quinone oxidoreductase-2) is an atypical oxidoreductase because no endogenous electron donor has been identified to date. The enzyme converts CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide], in the presence of the synthetic nicotinamide cofactor analog EP0152R, to a cytotoxic bifunctional alkylating agent. NQO2 activity in hepatocellular t ... [truncated at 450 characters in length]|
|Author||Middleton, Mark R; Knox, Richard; Cattell, Emma; et al|
|Subject||Adult Aged Antineoplastic Agents Aziridines Cell Death Cross-Linking Reagents Crystallography, X-Ray DNA, Neoplasm Enzyme Activation Female Humans Male Middle Aged Models, Molecular Neoplasms Prodrugs Quinone Reductases adverse effects chemistry pharmacokinetics therapeutic use adverse effects chemistry pharmacokinetics therapeutic use drug effects pharmacology metabolism drug effects drug therapy chemistry pharmacology therapeutic use chemistry metabolism|
A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date.
|Abstract||Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G > A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T > C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of het ... [truncated at 450 characters in length]|
|Author||Gregson, Celia L; Hollingworth, Peter; Williams, Martin; et al|
|Subject||Activin Receptors, Type I Adult Base Sequence DNA Mutational Analysis Female Heterozygote Humans Middle Aged Molecular Sequence Data Mutation Myositis Ossificans Ossification, Heterotopic Protein Structure, Tertiary Young Adult chemistry genetics genetics complications genetics complications genetics|
Selective inhibition of BET bromodomains.
|Abstract||Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of ... [truncated at 450 characters in length]|
|Author||Filippakopoulos, Panagis; Qi, Jun; Picaud, Sarah; et al|
|Subject||Amino Acid Sequence Animals Azirines Binding Sites Carcinoma, Squamous Cell Cell Differentiation Cell Line, Tumor Cell Proliferation Chromatin Dihydropyridines Female Humans Mice Mice, Nude Models, Molecular Molecular Sequence Data Nuclear Proteins Protein Binding Protein Structure, Tertiary Recombinant Proteins Sequence Alignment Skin Neoplasms Stereoisomerism Transcription Factors chemical synthesis chemistry pharmacology physiopathology drug effects drug effects metabolism chemical synthesis chemistry pharmacology antagonists and inhibitors metabolism drug effects metabolism physiopathology antagonists and inhibitors metabolism|