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Public Library of Science, PLoS ONE, 7(10), p. e0132455, 2015

DOI: 10.1371/journal.pone.0132455

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Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Insulin-Degrading-Enzyme (IDE) is a Zn 2+ -dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study, we examine the mechanistic and molecular features of IDE-26S proteasome interaction in a cell experimental model, extending the investigation also to the effect of IDE on the enzymatic activities of the 26S proteasome. Further, kinetic investigations indicate that the 26S proteasome activity undergoes a functional modulation by IDE through an extra-catalytic mechanism. The IDE-26S proteasome interaction was analyzed during the Heat Shock Response and we report novel findings on IDE intracellular distribution that might be of critical relevance for cell metabolism.