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STRATEGIES FOR THE PROCESSING OF PRO-OPIOMELANOCORTIN

STRATEGIES FOR THE PROCESSING OF PRO-OPIOMELANOCORTIN
阿片黑皮质素原的加工策略
批准号:
3235034
负责人:
ROBERT M DORES
金额:
$7.9万
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-06-01 至 1989-05-31

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中文摘要
翻译
阿黑皮素原是促肾上腺皮质激素和肾上腺皮质激素的共同前体, β-LPH相关多肽,可以经历多种翻译后 活动,以产生不同的最终产品集在不同地区的 哺乳动物垂体 这种生物合成途径也存在于 所有非哺乳类脊椎动物的代表,这些 系统可以提供独特的模型来研究不同的策略, 调节的生物合成和翻译后加工 阿黑皮素原(POMC)。 这些研究将探讨蛋白水解切割的机制, 四种不同的垂体中POMC相关产物的N-乙酰化 非哺乳类脊椎动物的一个种;爬行动物,Anolis carolinensis; 两栖动物,非洲爪蟾;原始硬骨鱼,Amia calva;和 圆口虫、海岩吸鳅(Petromyzonmarinus)。 提取物的稳态分析 垂体前叶和垂体中叶放射免疫测定法 凝胶过滤、离子交换和反相HPLC程序,以及 这些组织在培养中的体外脉冲放射性标记研究将提供 蛋白水解加工策略的广义系统发育观点 和POMC相关终产物的N-乙酰化。 背景适应和慢性应激对POMC的影响 垂体系统将在A. carolinensis和X.光滑。 这些研究将使用稳态分析和体外生物合成 标签程序,以研究这些范式对变化的影响, 合成的速率,翻译后加工的模式, POMC产物的分泌速率。 这些研究将审查不同的战略, 多蛋白质的差异加工,并将作为基础, 未来的项目,以深入了解影响 阿黑皮素原生物合成途径的进化。
英文摘要
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.
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