REGULATION OF PROTEIN SYNTHESIS AND ERYTHROPOIESIS

这项研究的长期目标是阐明 控制血红蛋白合成的机制，特别是其作用 血红素和蛋白质合成在调节珠蛋白合成中的作用 正常和异常红系细胞中的其他蛋白质及其定义 血红素在红系和红系分化成熟中的作用 其他真核细胞。具体目标包括澄清 蛋白合成启动的调控机制 磷酸化和去磷酸化，重点是血红素调节的 EIF-2的相互作用及其逆转作用 因子、因子及因子在eIF-2循环中的作用 血红素调节的eIF-2α激酶分子结构之间的关系 以及它的激活和活性，以及它的分布和功能 在红系细胞和非踝系细胞中有相同和相似的激酶。这 研究不仅与蛋白质合成的调节有关 一般在真核细胞中存在，但对 理解以血红素缺乏为特征的人类贫血，即， 缺铁性贫血是世界上最常见的疾病之一，铅 中毒，以及铁粒母细胞性贫血。方法论涉及到现场 以及参与蛋白质起始的成分的体外研究 血红素调节的eIF-2α蛋白的合成和纯化 并对其结构进行了分析。

The long-term objectives of this research are the elucidation of the mechanism controlling the synthesis of hemoglobin, especially the role of heme and of protein synthesis in regulating the synthesis of globin and other proteins in normal and abnormal erythroid cells, and the definition of the role of heme in the differentiation and maturation of erythroid and other eukaryotic cells. The specific aims include elucidation of the mechanisms of regulation of initiation of protein synthesis by phosphorylation and dephosphorylation, with emphasis on the heme-regulated elf-2 alpha protein kinase; the interaction of eIf-2 and the reversing factor, RF, and the role of RF in the recycling of eIF-2 the relationship between the molecular structure of the heme-regulated eIF-2 alpha kinase and its activation and activity, and the distribution and function of the same and similar kinases in erythroid and non-arythroid cells. This research is relevant not only to the regulation of protein synthesis generally in eukaryotic cells but specifically is significant for understanding human anemias characterized by heme deficiency, i.e., iron-lack anemia, one of the world's most prevalent disorders, lead poisoning, and the sideroblastic anemias. The methodology involves in situ and vitro studies of the components involved in initiation of protein synthesis, and the purification of the heme-regulated eIF-2 alpha kinase and analysis of its structure.