ENU mouse mutant with a hypomorphic mutation in DNA ligase IV
|Subject||Mice Abnormalities Genetic aspects DNA ligases Mutagenesis|
Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.
|Abstract||Much attention has recently been focused on PIM kinases as potential targets for the treatment of hematopoietic malignancies and some solid cancers. Using protein stability shift assays, we identified a family of imidazo[1,2-b]pyridazines to specifically interact with and inhibit PIM kinases with low nanomolar potency. The high-resolution crystal structure of a PIM1 inhibitor complex revealed that imidazo[1,2-b]pyridazines surprisingly interact w ... [truncated at 450 characters in length]|
|Author||Pogacic, Vanda; Bullock, Alex N; Fedorov, Oleg; et al|
|Subject||Animals Antineoplastic Agents Cell Line, Tumor Chemistry, Pharmaceutical Drug Design Enzyme Inhibitors Humans Inhibitory Concentration 50 Mice Models, Chemical Models, Molecular Protein Binding Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-pim-1 Pyridazines Structure-Activity Relationship pharmacology methods chemistry pharmacology antagonists and inhibitors antagonists and inhibitors chemistry|
Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector.
|Abstract||Regulator of G-protein signaling (RGS) proteins have been well-described as accelerators of Galpha-mediated GTP hydrolysis ("GTPase-accelerating proteins" or GAPs). However, RGS proteins with complex domain architectures are now known to regulate much more than Galpha GTPase activity. RGS14 contains tandem Ras-binding domains that have been reported to bind to Rap- but not Ras GTPases in vitro, leading to the suggestion that RGS14 is a Rap-specif ... [truncated at 450 characters in length]|
|Author||Willard, Francis S; Willard, Melinda D; Kimple, Adam J; et al|
|Subject||Animals Binding Sites Cell Differentiation Extracellular Signal-Regulated MAP Kinases Fibroblast Growth Factor 2 Humans Mice Mitogen-Activated Protein Kinases Multiprotein Complexes Nerve Growth Factor Neurites PC12 Cells Protein Binding RGS Proteins Rats raf Kinases ras Proteins antagonists and inhibitors physiology antagonists and inhibitors physiology physiology metabolism|
A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival.
|Abstract||Deficiency of the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase involved in isoleucine metabolism causes an organic aciduria with atypical neurodegenerative course. The disease-causing gene is HSD17B10 and encodes 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), a protein also implicated in the pathogenesis of Alzheimer's disease. Here we show that clinical symptoms in patients are not correlated with residual enzymatic act ... [truncated at 450 characters in length]|
|Author||Rauschenberger, Katharina; Schöler, Katja; Sass, Jörn Oliver; et al|
|Subject||3-Hydroxyacyl CoA Dehydrogenases Animals Apoptosis Cell Survival Cells, Cultured Fibroblasts Gene Deletion Genetic Complementation Test Humans Hydroxysteroid Dehydrogenases Infant Mice Mice, Knockout Mitochondria Models, Molecular Neurons Protein Structure, Tertiary Xenopus deficiency metabolism metabolism ultrastructure deficiency metabolism physiology ultrastructure physiology|
Conformational stability and activity of p73 require a second helix in the tetramerization domain.
|Abstract||p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additi ... [truncated at 450 characters in length]|
|Author||Coutandin, D; Löhr, F; Niesen, F H; et al|
|Subject||Amino Acid Sequence Animals Conserved Sequence DNA-Binding Proteins Humans Mice Models, Molecular Molecular Sequence Data Mutation Nuclear Magnetic Resonance, Biomolecular Nuclear Proteins Phosphoproteins Protein Multimerization Protein Structure, Quaternary Protein Structure, Secondary Sequence Alignment Thermodynamics Trans-Activators Tumor Suppressor Protein p53 Tumor Suppressor Proteins chemistry genetics metabolism chemistry genetics metabolism chemistry metabolism chemistry metabolism chemistry metabolism chemistry genetics metabolism|