Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene

The nucleotide sequence of Hs 3-PGDH gene, encoding human 3-phosphoglycerate dehydrogenase that catalyzes the initiating step in the phosphorylated pathway of serine biosynthesis, has been determined, The 3-PGDH gene has a predicted 533 amino acid open reading frame, encoding a 56.8 kDa protein that shares 94.0% similarity with rat-liver 3-PGDH, Two different transcripts corresponding to 3-PGDH mRNA were detected in human normal tissues. A dominant 2.1 kb transcript was expressed at high levels in prostate. testis, ovary, brain, liver, kidney, and pancreas, and weakly expressed in thymus, colon, and heart. A 710 bp transcript also appeared as a weaker band where the 2.1 kb mRNA was expressed, and it was more significant than the 2.1 kb mRNA in heart and skeletal muscle. The TPA-induced monocytic differentiation of U937, which also resulted in growth arrest, abruptly downregulated the expression of 3-PGDH. Removal of TPA restored cell growth through the retrodifferentiation process and subsequent expression of 3-PGDH. The 3-PGDH mRNA was markedly expressed in human leukemias, lymphoma Sup-T1, colon adenocarcinoma COLO 320DM, epitheloid carcinoma HeLa S3, and murine lymphoma BW5147.G.1.4, but not in human leukemia K562, This report demonstrates that the human 3-PGDH-gene is regulated at the transcriptional level depending on tissue specificty and cellular proliferative status, and its transcriptional regulation mechanism may be a useful target for diagnosis and therapy of cancer. (C) 2000 Elsevier Science B.V. All rights reserved.