THE ONCOFETAL PROTEIN P65 - A NEW MEMBER OF THE STEROID THYROID RECEPTOR SUPERFAMILY/

The 65-kDa oncofetal protein (p65), a potential tumor marker discovere d and characterized in our laboratory, is highly conserved in differen t species. Its amino acid composition, peptide map, and N-terminal and internal peptide sequences are very similar if not identical in human s and rodents. We have now identified the p65 gene as a novel member o f the superfamily of genes that encode nuclear receptors for various h ydrophobic ligands such as steroids, vitamin D, retinoic acid, and thy roid hormones. These receptors are composed of several domains importa nt in hormone binding, DNA binding, dimerization, and transcription ac tivation. The human p65 cDNA was partially cloned, revealing at its C- terminal end regulatory elements typical of this superfamily of genes. The DNA-binding domain coincides with the cysteine-rich region encomp assing the two conserved zinc fingers. In addition, the domain homolog ous to the receptor dimerization site was found close to the C-termina l end. The p65 protein is highly homologous to estrogen receptor in it s DNA-binding domain but not in other regions of the sequence, indicat ing that p65 is a new receptor with an as yet unknown ligand. In addit ion, we have identified in the cloned p65 cDNA fragment sequences enco ding two peptides, obtained by CNBr cleavage, whose amino acid sequenc es were previously established.