RESUMEN

The half-life of c- myc mRNA is regulated when cells change their growth rates or differentiate. Two regions within c- myc mRNA determine its short half-life. One is in the 3'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life. Here we report the cloning and further characterization of the mouse CRD-BP, a 577 amino acid protein containing four hnRNP K-homology domains, two RNP domains, an RGG RNA-binding domain and nuclear import and export signals. The CRD-BP is closely related to the chicken beta-actin zipcode-binding protein and is similar to three other proteins, one of which is overexpressed in some human cancers. Recombinant mouse CRD-BP binds specifically to c- myc CRD RNA in vitro and reacts with antibody against human CRD-BP. Most of the CRD-BP in the cell is cytoplasmic and co-sediments with ribosomal subunits.

Asunto(s)

Genes myc , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Secuencia de Bases , Sitios de Unión/genética , Línea Celular , Clonación Molecular , Citoplasma/metabolismo , Cartilla de ADN/genética , ADN Complementario/genética , Humanos , Ratones , Datos de Secuencia Molecular , Polirribosomas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homología de Secuencia de Aminoácido , Transfección