title: Degradation of the cleaved leader peptide of thiolase by a peroxisomal proteinase.
abstract: A peroxisomal location for insulin-degrading enzyme (IDE) has been defined by confocal immunofluorescence microscopy of stably transfected CHO cells overexpressing IDE and digitonin-permeabilization studies in normal nontransfected fibroblasts. The functional significance of IDE in degrading cleaved leader peptides of peroxisomal proteins targeted by the type II motif was evaluated with a synthetic peptide corresponding to the type II leader peptide of prethiolase. The peptide effectively competed for degradation and cross-linking of the high-affinity substrate 125I-labeled insulin to IDE. Direct proteolysis of the leader peptide of prethiolase was confirmed by HPLC; degradation was inhibited by immunodepletion with an antibody to IDE. Phylogenetic analysis of proteinases related to IDE revealed sequence similarity to mitochondrial processing peptidases.
authors.affiliation: Department of Anatomy-Cell Biology, McGill University, Montreal, PQ Canada.
authors.forename: F
authors.initials: F
authors.lastname: Authier
authors.forename: J J
authors.initials: JJ
authors.lastname: Bergeron
authors.forename: W J
authors.initials: WJ
authors.lastname: Ou
authors.forename: R A
authors.initials: RA
authors.lastname: Rachubinski
authors.forename: B I
authors.initials: BI
authors.lastname: Posner
authors.forename: P A
authors.initials: PA
authors.lastname: Walton
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D010450:Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010802:Phylogeny; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
chemical_list: D000906:Antibodies; D010455:Peptides; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D000101:Acetyl-CoA C-Acetyltransferase; D010450:Endopeptidases