title: Insulin-degrading enzyme (IDE): a novel heat shock-like protein.
abstract: Insulin-degrading enzyme (IDE) is a highly conserved zinc metallopeptidase that is ubiquitously distributed in human tissues, and particularly abundant in the brain, liver, and muscles. IDE activity has been historically associated with insulin and β-amyloid catabolism. However, over the last decade, several experimental findings have established that IDE is also involved in a wide variety of physiopathological processes, including ubiquitin clearance and Varicella Zoster Virus infection. In this study, we demonstrate that normal and malignant cells exposed to different stresses markedly up-regulate IDE in a heat shock protein (HSP)-like fashion. Additionally, we focused our attention on tumor cells and report that (i) IDE is overexpressed in vivo in tumors of the central nervous system (CNS); (ii) IDE-silencing inhibits neuroblastoma (SHSY5Y) cell proliferation and triggers cell death; (iii) IDE inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells. In this work, we propose a novel role for IDE as a heat shock protein with implications in cell growth regulation and cancer progression, thus opening up an intriguing hypothesis of IDE as an anticancer target.
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Via Montpellier 1, I-00133, Rome, Italy.
authors.forename: Grazia Raffaella
authors.initials: GR
authors.lastname: Tundo
authors.forename: Diego
authors.initials: D
authors.lastname: Sbardella
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianculli
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Desimio
authors.forename: Gaetano
authors.initials: G
authors.lastname: Arcuri
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Coletta
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D017124:Conserved Sequence; D015536:Down-Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007328:Insulin / Q000378:metabolism; D007339:Insulysin / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D045726:Metalloproteases / Q000737:chemistry; D008856:Microscopy, Fluorescence / Q000379:methods; D009447:Neuroblastoma / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors
chemical_list: D006360:Heat-Shock Proteins; D007328:Insulin; D034741:RNA, Small Interfering; D045726:Metalloproteases; D007339:Insulysin