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 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.
Doyle
G A
GA
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1400 University Avenue, Madison,WI 53706, USA.
Betz
N A
NA
Leeds
P F
PF
Fleisig
A J
AJ
Prokipcak
R D
RD
Ross
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011132:Polyribosomes / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C031192:oncofetal antigens