RESUMEN
14 patients with primary and recurrent herpetic keratitis were treated with continuous usage of human leukocyte interferon (HLI) at low concentration using therapeutic contact lenses. All patients recovered in a medium-short time of 7 days, including some who had not benefited by previous treatments (idoxuridine, etc.). We conclude that continuous application of HLI increases its effectiveness.
Asunto(s)
Lentes de Contacto , Interferón Tipo I/administración & dosificación , Queratitis Dendrítica/tratamiento farmacológico , Adolescente , Adulto , Ensayos Clínicos como Asunto , Úlcera de la Córnea/tratamiento farmacológico , Femenino , Humanos , Interferón Tipo I/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Factores de TiempoRESUMEN
Transcription factor c-Jun appears to be a nuclear target of the Ras-induced signal transduction pathway. In fact, some experiments show that transforming forms of the Ras protein cooperate with Jun in transcriptional activation mediated by an AP-1 site and others indicate that the two oncoproteins cooperate in cellular transformation. Although it is likely that intracellular signaling systems activated by Ras might act directly on c-Jun by inducing specific phosphorylation, it is unclear how c-Jun participates in the transformation process. Here, we present results obtained with a LexA-Jun zipper fusion that lacks both the transcriptional activation domains and the basic region of the DNA-binding domain of c-Jun and contains only the intact leucine-zipper domain. This fusion product has a dominant negative effect on the transcriptional activation elicited by phorbol esters, c-Jun, c-Fos, Ras and E1A on an AP-1-responsive site. An analogous LexA-Fos zipper fusion has similar effects on transcriptional induction. The LexA-Jun zipper fusion acts further as a transformation suppressor, since it causes the generation of nontransformed revertants of ras-transformed cells. This effect is likely to be elicited by the dimerization potential of the Jun leucine zipper trapping cellular Jun and/or Fos in a protein complex unable to bind to DNA. These data implicate further that Ras-mediated transformation involves functional transcription factor AP-1 and that it is possible to interfere with cell transformation by interfering simply with the dimerization of transcription factors involved in the transformation process.
Asunto(s)
Proteínas Bacterianas/metabolismo , Transformación Celular Neoplásica , Genes ras , Leucina Zippers/fisiología , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Represoras/metabolismo , Serina Endopeptidasas , Supresión Genética , Células 3T3 , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/genética , Cloranfenicol O-Acetiltransferasa/genética , Cloranfenicol O-Acetiltransferasa/metabolismo , Coriocarcinoma , Escherichia coli/genética , Genes Reguladores/efectos de los fármacos , Humanos , Leucina Zippers/genética , Ratones , Mutagénesis , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Recombinantes de Fusión/metabolismo , Mapeo Restrictivo , Acetato de Tetradecanoilforbol/farmacología , TransfecciónRESUMEN
Mammalian spermatogenesis consists of a series of complex developmental processes controlled by the pituitary-hypothalamic axis. This flow of biochemical information is directly regulated by the adenylate cyclase signal transduction pathway. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response. Here we report the expression of a novel CREM isoform (CREM tau) in adult testis. CREM tau differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREM tau activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.
Asunto(s)
Encéfalo/fisiología , Proteínas de Unión al ADN/genética , Proteínas Represoras , Espermatogénesis , Testículo/fisiología , Envejecimiento , Secuencia de Aminoácidos , Síndrome de Resistencia Androgénica/genética , Animales , Secuencia de Bases , Encéfalo/crecimiento & desarrollo , Modulador del Elemento de Respuesta al AMP Cíclico , ADN/genética , ADN/aislamiento & purificación , Proteínas de Unión al ADN/fisiología , Masculino , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Especificidad de Órganos , Poli A/genética , Poli A/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , ARN/genética , ARN/aislamiento & purificación , ARN Mensajero/genética , Homología de Secuencia de Ácido Nucleico , Maduración Sexual , Testículo/crecimiento & desarrolloRESUMEN
Ras proteins are membrane-associated transducers of eternal stimuli to unknown intracellular targets. The constitutively activated v-ras oncogene induces dedifferentiation in thyroid cells. v-Ras appears to act by stimulating protein kinase C (PKC), which inhibits the nuclear migration of the catalytic subunit of the cAMP-dependent protein kinase A (PKA). Nuclear tissue-specific and housekeeping trans-acting factors that are dependent on phosphorylation by PKA are thus inactivated. Exclusion of the PKA subunit from the nucleus could represent a general mechanism for the pleiotropic effects of Ras and PKC on cellular growth and differentiation.