title: Proteolytic activation of human procathepsin D.
abstract: Procathepsin D is a short-lived inactive precursor of the lysosomal aspartyl protease, cathepsin D. Pulse-chase analysis using radiolabeled amino acids demonstrated the existence of several biosynthetic intermediates during formation of mature cathepsin D (summarized in Figure 1). Procathepsin D is capable of autocatalytic cleavage to pseudocathepsin D. This was demonstrated using small quantities of procathepsin D isolated from cell culture media as well as using a non-glycosylated form of procathepsin D synthesized in a bacterial expression system. Complete conversion to the single-chain cathepsin D appears to require a second enzyme which is inhibited by leupeptin. This conclusion was drawn from the inability to produce single-chain enzyme from either procathepsin D or pseudocathepsin D in vitro as well as observations from addition of protease inhibitors to cell cultures. It appears that the conversion of procathepsin D to active single-chain enzyme falls between the paradigms of pepsinogen autoactivation and prorenin conversion by a separate enzyme.
authors.affiliation: Department of Cell Biology and Anatomy, University of Miami School of Medicine, Florida.
authors.forename: G
authors.initials: G
authors.lastname: Richo
authors.forename: G E
authors.initials: GE
authors.lastname: Conner
mesh_terms: D000595:Amino Acid Sequence; D002402:Cathepsin D / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D010447:Peptide Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D004792:Enzyme Precursors; D009842:Oligopeptides; D010447:Peptide Hydrolases; C058345:procathepsin D; D002402:Cathepsin D