THE C-MYC CODING REGION DETERMINANT-BINDING PROTEIN - A MEMBER OF A FAMILY OF KH DOMAIN RNA-BINDING PROTEINS

The half-life of c-myc mRNA is regulated when cells change their growt h 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 determina nt-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 c haracterization of the mouse CRD-BP, a 577 amino acid protein containi ng four hnRNP K-homology domains, two RNP domains, an RGG RNA-binding domain and nuclear import and export signals. The CRD-BP is closely re lated to the chicken p-actin zipcode-binding protein and is similar to three other proteins, one of which is overexpressed in some human can cers. 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-B P in the cell is cytoplasmic and co-sediments with ribosomal subunits.