Prolyl Endopeptidase Cleaves the Apoptosis Rescue Peptide Humanin and Exhibits an Unknown Post-Cysteine Cleavage Specificity
The data presented, demonstrate for the first time PEP turnover of HN by a limited postcysteine as well as the expected post-proline proteolysis demonstrated in cell extract resulting in the inactivation of this potentially apoptosis-related factor. These findings lead to the hypothesis of a PEP-mediated control of HN homeostasis maintaining neuronal cell survival. This implicates a novel use of PEP inhibitors potentially preventing intracellular HN digestion. Consequently, PEP-inhibition might be a new target for apoptosis prevention.
This study further uncovered a so far unknown enzymatic specificity for a post-cysteine cleavage of the mammalian exopeptidases DP2, DP4, DP8 and DP9 and the endopeptidase PEP.
KeywordsDipeptidyl Peptidase Prolyl Endopeptidase Prolyl Oligopeptidase Prolyl Endopeptidase Inhibition Apoptosis Prevention
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