REGULATION OF PROTEIN SYNTHESIS AND ERYTHROPOIESIS

蛋白质合成和红细胞生成的调节

• 批准号: 3225563
• 负责人: IRVING M LONDON
• 金额: $ 27.42万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225563
• 关键词: cell differentiation; chemical binding; chromatography; erythrocytes; erythroleukemia; erythropoiesis; eukaryote; gel electrophoresis; genetic manipulation; globin; heme; hemoglobin; hemoprotein biosynthesis; human tissue; immunofluorescence technique; iron disorder; laboratory mouse; laboratory rabbit; lead poisoning; messenger RNA; molecular cloning; monoclonal antibody; nucleic acid probes; phosphorylation; protein biosynthesis; protein kinase; protein sequence; reticulocytes; sideroblastic anemia; tissue /cell culture

The long-term objectives of this research are the elucidation of the regulation of hemoglobin synthesis in normal and abnormal hematologic conditions; emphasis is placed on the translational control of the synthesis of globin and other proteins in erythroid cells by heme and eIF- 2alpha kinases and on the relationship of this control to erythroid cell development and maturation. The specific aims include elucidation of: the structure-function relations of heme-regulated and double-stranded RNA activated eIF-2alpha kinase in the human hematologic disorders characterized by heme-deficiency. This research is relevant to eukaryotic cells generally and specifically it is significant for understanding the human anemias in which heme-deficiency occurs: iron-lack anemia, one of the most prevalent world-wide disorders, the anemia of lead poisoning, and the sideroblastic anemias. The experimental design and methods involve: the study of protein synthesis in situ in rabbit reticulocytes and their lysates and in vitro in components of these cells; the purification of the heme-regulated eIF-2alpha kinase; the study of the effects of heme and other metalloporphyrins on the eIF-2alpha kinase; and the cloning of the cDNAs of the eIF-2alpha kinases, the determination of their amino acid sequences and their ATP binding sites; the preparation of polyclonal and monoclonal antibodies to the eIF-2alpha kinases and the determination by immunofluorescence of the presence of the eIF-2alpha kinases in erythroid cells at different stages of development in normal man and in the heme- deficiency clinical disorders.

本研究的长期目标是阐明