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

PLoS One. 2015 Jul 17;10(7):e0132455. doi: 10.1371/journal.pone.0132455. eCollection 2015.

Abstract

Insulin-Degrading-Enzyme (IDE) is a Zn2+-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Complex Mixtures
  • Endoplasmic Reticulum / metabolism
  • Gene Silencing
  • Heat-Shock Response
  • Humans
  • Insulysin / metabolism*
  • Neuroblastoma / enzymology
  • Neuroblastoma / pathology
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • Stress, Physiological
  • Subcellular Fractions / metabolism
  • Time Factors

Substances

  • Complex Mixtures
  • Insulysin
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease

Grants and funding

The financial support is from the Italian Ministry of the University and Research (MiUR FIRB RBNE03PX83 to M.C.) and the Italian Space Agency (ASI SMEMCO n. DC-DTE-2011-033 to U.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.