RESUMO
OBJECTIVE: Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS. METHODS: We assessed the polyQ lengths of ataxin 1, ataxin 3, ataxin 6, ataxin 7, TBP, atrophin 1, and huntingtin in several hundred patients with sporadic ALS and healthy controls. RESULTS: Other than ataxin 2, we did not identify a significant association with the other polyQ genes and ALS. CONCLUSIONS: These data indicate that the effects of ataxin 2 polyQ expansions on ALS risk are likely to be rooted in the biology of ataxin 2 or ataxin 2-specific interactions, rather than the presence of an expanded polyQ repeat per se. These findings have important consequences for understanding the role of ataxin 2 in ALS pathogenesis and provide a framework for future mechanistic studies.
Assuntos
Esclerose Lateral Amiotrófica/genética , Expansão das Repetições de DNA/genética , Peptídeos/genética , Ataxina-1 , Ataxina-3 , Ataxina-7 , Ataxinas , Canais de Cálcio/genética , Humanos , Proteína Huntingtina , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Proteína de Ligação a TATA-Box/genéticaAssuntos
Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/genética , Crista Neural/embriologia , Semaforina-3A , Fatores de Transcrição , Animais , Proteínas de Transporte/genética , Movimento Celular , Proteínas de Ligação a DNA/genética , Síndrome de DiGeorge/embriologia , Síndrome de DiGeorge/genética , Modelos Animais de Doenças , Dupla Via de Saída do Ventrículo Direito/embriologia , Dupla Via de Saída do Ventrículo Direito/genética , Genes da Neurofibromatose 1 , Humanos , Camundongos , Mutação , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Crista Neural/citologia , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados , Proteínas com Domínio T/genéticaRESUMO
We describe here the first full-length sequence of a member of a novel gene family encoding a protein in the mouse that we call Lupin. Lupin is homologous to a human protein previously called p36, which was purified from alpha-interferon-treated cells that formed lupus inclusions. Lupus inclusions are dense intracellular deposits found in endothelial cells and lymphocytes of patients with systemic lupus erythematosis and AIDS. Proteins closely related to Lupin exist in evolutionarily divergent species including Caenorhabditis elegans, Drosophila and zebrafish. At least one other lupin-related gene is expressed in the mouse and in man. Lupin is expressed in mouse embryos and adults, notably in liver, spleen, central nervous system, multiple epithelia and all types of muscle. In skeletal muscle, expression analysis suggests that Lupin associates with the contractile apparatus.
Assuntos
Família Multigênica , Proteínas/genética , 5'-Nucleotidase , Sequência de Aminoácidos , Animais , Clonagem Molecular , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lupinus , Camundongos , Dados de Sequência Molecular , Proteínas/química , Proteínas/metabolismo , Homologia de Sequência de AminoácidosRESUMO
The structure of apakaochtodene A, the minor isomer of two tetrahalogenated ochtodene monoterpenes, isolated from the red marine alga Portieria hornemannii (Lyngbye) Silva has been identified as 6(S)-bromo-1,4(S),8(R)-trichloro-2(Z)-ochtodene (1) by NMR spectral and X-ray crystallographic analysis. Its geometrical isomer, apakaochtodene B (2), which could not be separated from 1 and thus characterized as a 95:5 mixture of 2:1 had (1)H and (13)C NMR spectral characteristics similar to previously known ochtodene (3) and the related tetrahalogenated monoterpene 4.
Assuntos
Monoterpenos , Rodófitas/química , Terpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Biologia Marinha , Estrutura Molecular , Terpenos/químicaRESUMO
Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship studies led to a potent and selective inhibitor, HR-11, which blocks Ras farnesylation in vitro with an IC50 of 1.2 nM. The cell permeable methyl ester derivative of HR-11, HR-12, inhibits Ras farnesylation in intact cells with an IC50 of 10 microM and with no detectable inhibition of Rap1A/K-rev geranyl-geranylation.
