REGULATION OF ALPHA-FETOPROTEIN GENE EXPRESSION

α-胎蛋白基因表达的调节

• 批准号: 3482562
• 负责人: SHIRLEY M. TILGHMAN
• 金额: $ 38.47万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482562
• 关键词: DNA; Escherichia coli; affinity chromatography; alpha fetoprotein; bacteriophage lambda; basement membrane; cell growth regulation; chemical fingerprinting; clone cells; density gradient ultracentrifugation; developmental genetics; electron microscopy; embryo /fetus; embryo /fetus protein; gel electrophoresis; gene duplication; gene expression; genetic manipulation; genetic mapping; genetic recombination; genetic transcription; hamsters; hepatocellular carcinoma; hybrid cells; laboratory mouse; liver; liver cells; mature animal; messenger RNA; molecular cloning; neoplasm /cancer immunology; nucleic acid hybridization; nucleic acid sequence; protein biosynthesis; radiotracer; serum albumin; teratoma; tritium; vitelline membrane

The major protein component in the serum of the developing mammalian fetus is alpha-fetoprotein (AFP), which is synthesized in the embryonic liver and visceral endoderm of the yolk sac. After birth, the rate of synthesis of AFP in liver decreases drastically to levels that are barely detectable in nonpregnant adults. Synthesis of AFP is resumed in adult liver during liver regeneration and in specific tumors such as hepatomas and teratocarcinomas. In contrast, serum albumin, which is the major serum protein synthesized by the adult liver, increases from low levels early in development, to high, relatively constant levels after birth and in adult life. These serum proteins arose in evolution as the consequence of a gene duplication and are tightly linked in tandem on chromosome 5 in mice. Two transacting regulatory genes that affect AFP, but not albumin transcription in developing liver, have been described genetically. These genes recently have been shown to be pleiotrophic in that they affect transcription of other unlinked genes in addition to AFP. We are currently developing genetic and biochemical assays for the products of these regulatory genes that will allow us to isolate them and determine their mode of action. At the same time, the DNA sequences required for tissue-specific transcription of the AFP and albumin genes in vivo, using DNA-mediated gene transfer into both F9 teratocarcinoma cells and fertilized mouse eggs, are being identified. (M)

哺乳动物胎儿血清中的主要蛋白质成分