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. 1995 Apr 25;92(9):3859–3863. doi: 10.1073/pnas.92.9.3859

Degradation of the cleaved leader peptide of thiolase by a peroxisomal proteinase.

F Authier 1, J J Bergeron 1, W J Ou 1, R A Rachubinski 1, B I Posner 1, P A Walton 1
PMCID: PMC42061  PMID: 7731996

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.

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