title: Nonhuman cells correctly sort and process the human lysosomal enzyme cathepsin D.
abstract: Cathepsin D, like most lysosomal enzymes, undergoes multiple proteolytic cleavages during its lifetime. Although the significance of the earliest cleavages of cathepsin D is apparent (loss of the NH2-terminal signal peptide and activation peptide), functions of the two later cleavages are not understood and do not occur in all species. To examine these later events, a cDNA coding for human cathepsin D, which is normally processed to a two-chain form, was isolated and then expressed in mammalian cells from species which do not process the enzyme to the two-chain form. Analysis of the expressed human cathepsin D demonstrated proteolytic processing identical with that seen in normal human fibroblasts. Since processing to the two-chain form of the enzyme occurs in the lysosome, these studies revealed that the human cathepsin D was correctly sorted. The data also indicated that the sorting mechanism was conserved between diverse species and that late proteolytic processing in a variety of species was not determined by the presence or absence of the processing enzymes in the cell.
authors.affiliation: Department of Anatomy and Cell Biology, University of Miami School of Medicine, Florida 33101.
authors.forename: G E
authors.initials: GE
authors.lastname: Conner
authors.forename: J A
authors.initials: JA
authors.lastname: Udey
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.forename: J
authors.initials: J
authors.lastname: Sola
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D013045:Species Specificity
chemical_list: D004247:DNA; D002402:Cathepsin D