RESUMEN
The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-kappaB activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-kappaB and apoptotic signaling pathways and may be a component of the host innate immune response.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Apoptosis , Proteínas de Caenorhabditis elegans , Proteínas de Unión al Calcio/metabolismo , Proteínas Portadoras/metabolismo , Proteínas del Helminto/metabolismo , FN-kappa B/metabolismo , Proteínas/metabolismo , Secuencia de Aminoácidos , Factor Apoptótico 1 Activador de Proteasas , Secuencia de Bases , Proteínas Portadoras/genética , ADN Complementario , Humanos , Datos de Secuencia Molecular , Proteína Adaptadora de Señalización NOD1 , Homología de Secuencia de Aminoácido , Transducción de SeñalRESUMEN
We isolated a mutant defective in C-terminal farnesyl cysteine:carboxyl methyltransferase activity from a screen for mutations causing a-specific sterility. A genomic fragment was cloned from a yeast multi-copy library that restored mating. Both the cloned gene and the sterile mutation were allelic to the STE14 gene. A ste14-complementing 2.17 kb BamHI fragment subclone was sequenced and found to encode a 239 amino acid protein with a molecular weight of 27,887 Daltons. The hydrophobicity profile of the methyltransferase reveals the presence of at least five potential transmembrane domains. In comparisons of the C-terminal methyltransferase amino acid sequence with those in the PIR and Swiss protein databases, no significantly similar sequences were found nor were conserved regions from other methyltransferases present.
Asunto(s)
Genes Fúngicos/genética , Proteína Metiltransferasas/genética , Prenilación de Proteína/genética , Saccharomyces cerevisiae/genética , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica) , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Prueba de Complementación Genética , Biblioteca Genómica , Metiltransferasas/genética , Datos de Secuencia Molecular , Mapeo Restrictivo , Saccharomyces cerevisiae/enzimología , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
We present the genetic analysis of a large number of mutations in the outside end of insertion sequence IS10. (i) The terminal inverted repeat sequence is probably the primary site of transposase binding. Mutations in this region fall into phenotypic classes which correspond to their map locations, suggesting that this region may consist of several distinct functional segments. Similarities between the organization of IS10's inverted repeat and those of other transposable elements are discussed. (ii) Base pairs 23-42 include a consensus binding sequence for one of the IS10 transposition host factors, IHF. The phenotypes of mutations in this region suggest that IHF is the major host factor for outside-end transposition activity in vivo and that base pairs throughout this region are important for the IHF interaction. (iii) Mutations in bp 43-61 do not affect outside-end transposition activity but do affect, in expected ways, previously identified determinants involved in expression and regulation of transposase. (iv) Some mutations in bp 23-42 also affect transposase expression; the possibility that IHF negatively regulates transcription initiation is discussed.