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 beta-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.

Tundo, G.r., Sbardella, D., Ciaccio, C., Bianculli, A., Orlandi, A., Desimio, M.g., et al. (2013). Insulin-degrading enzyme (IDE): A novel heat shock-like protein. JOURNAL OF BIOLOGICAL CHEMISTRY, 288(4), 2281-2289 [10.1074/jbc.M112.393108].

Insulin-degrading enzyme (IDE): A novel heat shock-like protein

Tundo G. R.;Sbardella D.;Ciaccio C.;Orlandi A.;Desimio M. G.;Coletta M.;Marini S.
2013-01-01

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 beta-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.
2013
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Conserved Sequence; Down-Regulation; Heat-Shock Proteins; Humans; Immunohistochemistry; Insulin; Insulysin; Jurkat Cells; Metalloproteases; Microscopy, Fluorescence; Neuroblastoma; RNA, Small Interfering; Time Factors
Tundo, G.r., Sbardella, D., Ciaccio, C., Bianculli, A., Orlandi, A., Desimio, M.g., et al. (2013). Insulin-degrading enzyme (IDE): A novel heat shock-like protein. JOURNAL OF BIOLOGICAL CHEMISTRY, 288(4), 2281-2289 [10.1074/jbc.M112.393108].
Tundo, Gr; Sbardella, D; Ciaccio, C; Bianculli, A; Orlandi, A; Desimio, Mg; Arcuri, G; Coletta, M; Marini, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/229056
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