title: Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.
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.
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Sbardella
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Grazia Raffaella
authors.initials: GR
authors.lastname: Tundo
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR), Università Cattolica del Sacro Cuore, Largo F. Vito 1, I-00168, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sciandra
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Largo F. Vito 1, I-00168, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bozzi
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR), Università Cattolica del Sacro Cuore, Largo F. Vito 1, I-00168, Rome, Italy; School of Biochemistry, Medical Sciences Building, University Walk, Bristol, B581TD, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy; Center for Space Biomedicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D045424:Complex Mixtures; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020868:Gene Silencing; D018869:Heat-Shock Response; D006801:Humans; D007339:Insulysin / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D013312:Stress, Physiological; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
chemical_list: D045424:Complex Mixtures; D007339:Insulysin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease