STRATEGIES FOR THE PROCESSING OF PRO-OPIOMELANOCORTIN

点击翻译按钮获取中文摘要

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.