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FOLATE BINDERS IN HEMATOPOIESIS & CELL REPLICATION

造血中的叶酸结合剂

基本信息

批准号：
3170320
负责人：
SHELDON P ROTHENBERG
金额：
$ 2.95万
依托单位：
SUNY DOWNSTATE MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-05-01 至 1993-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3170320
关键词：
aplastic anemia autoradiography binding proteins biological polymorphism cell biology cell growth regulation cell transformation chemical structure function cytogenetics deficient growth media dementia dyserythropoietic anemia electron microscopy folate folate deficiency fragile X syndromes gel electrophoresis gene expression genetic library genetic manipulation genetic mapping hematopoiesis human population genetics human subject immunochemistry immunoprecipitation laboratory mouse laboratory rabbit ligands membrane activity membrane proteins molecular cloning monoclonal antibody neoplastic cell culture for noncancer research nucleic acid probes nucleic acid sequence nutrition related tag protein biosynthesis protein metabolism protein sequence radiotracer schizophrenia tissue /cell culture vitamin metabolism

项目摘要

A number of human diseases have been described which are not due to a quantitative deficiency of folic acid but which may respond to large doses of the vitamin. These include hematopoietic disorders, such as some forms of aplastic anemia, a hereditary form of dyserythropoiesis, neurologic disorders such as dementia, some forms of schizophrenia, the recently recognized fragile X chromosome syndrome, and drug induced disorders of folate metabosism. The response to large doses of folate suggests that a common defect may underlie these disorders. The folate binding proteins (FBPs) which have now been identified in the membrane, in the soluble, and most recently in the nuclear fraction of mammalian cells could be the common link. Most of the work on these proteins from mammalian cells have focused on their structural properties rather than on their function and turnover in the cell. In addition, there have been no studies on the molecular genetics of the FBP to characterize the structure, organization and expression of the gene. The primary aims of this project, therefore, are to establish the precise function(s) of the folate binding proteins (FBPs) in the cellular uptake and intracellular metabolism of folate and to characterize fully the molecular genetics of this protein(s). The experiments will be designed to achieve the following objectives: 1) define the kinetics for the synthesis and degradation of the FBP in human KB cells and study the factors that affect these parameters using intrinsic labeling with (35S)methionine 2) map the cellular and topographic distribution of the FBP in the KB cell using electron microscopy immunocytology and study the factors that modify this distribution using monoclonal antibodies 3) clone the FBP gene from KB cells and then characterize its organization and nucleotide sequence, determine its chromosomal location, and examine different human cell lines and tissues for expression and restriction fragment length polymorphism of the gene 4) determine if transfection of the functional FBP gene into cells which express little or no FBP improves the viability of these cells in folate deficient medium. The study could provide definitive evidence that the FBP provides a critical function in cellular metabolism.

一些人类疾病已经被描述，但它们不是