The oncofetal protein p65: a new member of the steroid/thyroid receptor superfamily.
The 65-kDa oncofetal protein (p65), a potential tumor marker discovered and characterized in our laboratory, is highly conserved in different species. Its amino acid composition, peptide map, and N-terminal and internal peptide sequences are very similar if not identical in humans and rodents. We have now identified the p65 gene as a novel member of the superfamily of genes that encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid, and thyroid hormones. these receptors are composed of several domains important in hormone binding, DNA binding, dimerization, and transcription activation. 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 encompassing the two conserved zinc fingers. In addition, the domain homologous to the receptor dimerization site was found close to the C-terminal end. The p65 protein is highly homologous to estrogen receptor in its DNA-binding domain but not in other regions of the sequence, indicating that p65 is a new receptor with an as yet unknown ligand. In addition, we have identified in the cloned p65 cDNA fragment sequences encoding two peptides, obtained by CNBr cleavage, whose amino acid sequences were previously established.
Hanausek
M
M
University of Texas M. D. Anderson Cancer Center, Smithville 78957, USA.
Szemraj
J
J
Adams
A K
AK
Walaszek
Z
Z
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D029543:Nucleocytoplasmic Transport Proteins; D051381:Rats; D011987:Receptors, Steroid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018076:DNA, Complementary; C484020:HSAJ2425 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; C063447:p65 oncofetal mRNA transport protein, rat