The tissue-specific processing of Pro-ACTH/Endorphin recent advances and unsolved problems.

Pro-ACTH/endorphin (also called proopiomelanocortin) synthesis in corticotropes and melanotropes continues to serve as a model for investigating the series of enzymatic steps that convert inactive preprohormones to product peptides during transit of the molecules from the rough endoplasmic reticulum through the Golgi and into secretory granules. The complexity of the biosynthesis of bioactive peptides is increased by the widespread occurrence of tissue-specific and developmentally regulated posttranslational processing. Transfection of cDNAs encoding wild-type and mutant preproneuropeptide Y into AtT-20 corticotrope tumor cells revealed the importance of primary sequence in determining the extent of cleavage of the peptide precursor. The purification and cloning of several peptide-processing enzymes, including KEX-1, KEX-2, carboxypeptidase E, and peptidyl-glycine alpha-amidating monooxygenase, have provided important information about intracellular peptide processing, and are beginning to provide information about the sorting of soluble and membrane-associated components of secretory granules.