Caeruloplasmin biosynthesis by the human uterus.
The blue copper protein caeruloplasmin is synthesized mainly by hepatocytes. An alternative transcript for caeruloplasmin produced in certain extrahepatic tissues, CP-1, contains an additional 12 nucleotides encoding 4 amino acids not present in the hepatic transcript, CP-2 [Yang, Friedrichs, Cupples, Bonifacio, S Sanford, Horton & Bowman (1990) J. Biol. Chem. 265, 10780-10785]. We have demonstrated transcription of caeruloplasmin mRNA by a well-differentiated human uterine epithelial adenocarcinoma cell line, Ishikawa, and by human uterine endometrium and purified endometrial glands. Identical CP-2 nucleotide sequences were obtained for partial caeruloplasmin transcripts from human liver and Ishikawa cells, indicating that CP-2 transcripts are produced by uterine epithelial lining cells. The synthesis of caeruloplasmin protein was demonstrated for Ishikawa cells and another uterine adenocarcinoma cell line, ECC1. Peptide-mapping analysis indicated that caeruloplasmin secreted by Ishikawa cells was structurally identical with the protein synthesized by the human hepatoblastoma cell line HepG2. The secretion of a 135,000-M(r) caeruloplasmin by Ishikawa and ECC1 cells, comparable with that of the human hepatoblastoma cell line, HepG2, indicated similar processing of uterine and hepatic caeruloplasmin. Incorporation of 67Cu into caeruloplasmin was demonstrated for Ishikawa and ECC1 cells, suggesting that the human uterus produces a bioactive form of caeruloplasmin and possesses the necessary metal transporters and intracellular machinery for copper incorporation into this protein.
Schilsky
M L
ML
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.
Stockert
R J
RJ
Pollard
J W
JW
D001483:Base Sequence; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000096:biosynthesis* / Q000235:genetics; D003300:Copper / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000502:physiology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010449:Peptide Mapping; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014599:Uterus / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003300:Copper; D002570:Ceruloplasmin