The c-myc coding region determinant-binding protein: A member of a family of KH domain RNA-binding proteins

Abstract

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 β-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.