STRATEGIES FOR THE PROCESSING OF PRO-OPIOMELANOCORTIN

ACTH-和ACTH的共同前体--前阿片黑素皮质素 β-LPH相关多肽，可经历多种翻译后 在不同地区产生不同最终产品集的活动 哺乳动物的脑下垂体。这种生物合成途径也在 所有种类的非哺乳动物脊椎动物的代表，以及这些 系统可以为研究不同的策略提供独特的模型 调控蛋白质的生物合成和翻译后加工 前阿片黑素皮质素(POMC)。 这些研究将探索蛋白质水解性切割的机制和 四种不同品种大鼠脑垂体POMC相关产物的N-乙酰化 非哺乳类脊椎动物的物种；爬行动物，卡罗林鱼； 两栖动物非洲爪哇；原始硬骨鱼Amia Calva；以及 Cyclstome，Petromyzon marinus。黄连提取物的稳态分析 放射免疫法测定垂体前叶和中间叶 凝胶过滤、离子交换和反相高效液相程序，以及 对培养中的这些组织进行体外脉冲放射性标记研究将提供 蛋白质降解加工策略的广泛系统发生学观点 和POMC相关终端产品的N-乙酰化。 背景适应和慢性应激对POMC的影响 将对卡罗琳黑线姬鼠和莱维氏X.laevis的脑垂体系统进行研究。 这些研究将使用稳态分析和体外生物合成。 标记程序来研究这些范例对变化的影响 合成的速度、翻译后处理的模式以及 POMC产品的分泌率。 这些研究将考察监管的不同战略 多聚蛋白质的差异处理，并将作为基础 未来的项目，以深入了解影响 前阿片黑素皮质素生物合成途径的研究进展。

The polyprotein, pro-opiomelanocortin, the common precursor for ACTH- and beta-LPH-related polypeptides, can undergo a variety of post-translational events to yield distinct sets of end products in different regions of the mammalian pituitary. This biosynthetic pathway is also found in representatives of all the classes of non-mammalian vertebrates, and these systems may provide unique models for studying different strategies for regulating the biosynthesis and post-translational processing of pro-opiomelanocortin (POMC). These studies will investigate the mechanisms for proteolytic cleavage and N-acetylation of POMC-related products in the pituitaries of four diverse species of non-mammalian vertebrates: the reptile, Anolis carolinensis; the amphibian, Xenopus laevis; the primitive bony fish, Amia calva; and the cyclostome, Petromyzon marinus. Steady state analysis of extracts of anterior and intermediate pituitary by radioimmunoassay in conjunction with gel filtration, ion exchange and reverse phase HPLC procedures, and in vitro pulse radiolabeling studies of these tissues in culture will provide a broad phylogenetic view of the strategies for the proteolytic processing and N-acetylation of POMC-related end products. The effects of background adaptation and chronic stress on the POMC pituitary systems will be investigated in A. carolinensis and X. laevis. These studies will use steady state analysis and in vitro biosynthetic labeling procedures to study the effects of these paradigms on changes in the rate of synthesis, patterns of post-translational processing, and the rate of secretion of POMC products. These studies will examine different strategies for the regulation of differential processing of a polyprotein, and will serve as a basis for future projects to gain insights into the mechanisms that have influenced the evolution of the pro-opiomelanocortin biosynthetic pathway.