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

Diego Sbardella, Grazia Raffaella Tundo, Francesca Sciandra, Manuela Bozzi, Magda Gioia, Chiara Ciaccio, Umberto Tarantino, Andrea Brancaccio, Massimo Coletta, Stefano Marini

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)
274 Downloads (Pure)

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.
Original languageEnglish
Article numbere0132455
Number of pages21
JournalPLoS ONE
Volume10
Issue number7
DOIs
Publication statusPublished - 17 Jul 2015

Keywords

  • Blotting, Western
  • Cell Line, Tumor
  • Complex Mixtures
  • Endoplasmic Reticulum
  • Gene Silencing
  • Heat-Shock Response
  • Humans
  • Insulysin
  • Neuroblastoma
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Stress, Physiological
  • Subcellular Fractions
  • Time Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

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