https://www.ncbi.nlm.nih.gov/gene/3416
- Official Symbol
- IDEprovided by HGNC
- Official Full Name
- insulin degrading enzyme
- Primary source
- Also known as
- INSULYSIN
- Summary
- This gene encodes a zinc metallopeptidase that degrades intracellular insulin, and thereby terminates insulins activity, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. The preferential affinity of this enzyme for insulin results in insulin-mediated inhibition of the degradation of other peptides such as beta-amyloid. Deficiencies in this protein's function are associated with Alzheimer's disease and type 2 diabetes mellitus but mutations in this gene have not been shown to be causitive for these diseases. This protein localizes primarily to the cytoplasm but in some cell types localizes to the extracellular space, cell membrane, peroxisome, and mitochondrion. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but have not been experimentally verified.[provided by RefSeq, Sep 2009]
- Expression Ubiquitous expression in skin (RPKM 17.4), testis (RPKM 9.9) and 25 other tissues See more
- Preferred Names
- insulin-degrading enzyme
- Names
- Abeta-degrading protease
- insulin protease
- insulinase
- Ref.
PLoS One. 2015 Jul 17;10(7):e0132455. doi: 10.1371/journal.pone.0132455. eCollection 2015. Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.
Sbardella D1, Tundo GR1,et.el. 1.
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.
2 results
Insulin Inhibits the Ubiquitin-Dependent Degrading ...
Insulin Inhibits the Ubiquitin-Dependent Degrading ...A major metabolic effect of insulin is inhibition of cellular proteolysis, but the proteolytic systems involved are unclear. Tissues have multiple proteolytic systems, including the ATP- and ubiquitin-dependent proteasome pathway. The effect of insulin on this pathway was examined in vitro and in cultured cells. Insulin inhibited ATP- and ubiquitin-dependent lysozyme degradation more than 90% by reticulocyte extract, in a dose-dependent manner (IC50 approximately 50 nM). Insulin did not reduce the conjugation of ubiquitin to lysozyme and was not itself ubiquitin-conjugated. In HepG2 cells, insulin increased ubiquitin-conjugate accumulation 80%. The association between the 26S proteasome and an intracellular protease, the insulin-degrading enzyme (IDE), was examined by a purification scheme designed to enrich for the 26S proteasome. Copurification of IDE activity and immunoreactivity with the proteasome were detected through several chromatographic steps. Glycerol gradient analysis revealed cosedimentation of IDE with the 20S proteasome and possibly with the 26S proteasome. The proteasome-associated IDE was displaced when the samples were treated with insulin. These results suggest that insulin regulates protein catabolism, at least in part, by decreasing ubiquitin-mediated proteasomal activity, and provides a new target for insulin action. The displacement of IDE from the proteasome provides a mechanism for this insulin action.
... IDE and the proteasome co-purify through a number of chromatographic steps (Duckworth et al. 1994, Bennett et al. 2000b). When IDE is either removed from the proteasome or inhibited, insulin has no influence on proteasome activity (Duckworth et al. 1994, 1998a, Hamel et al. 1998). ...
Miten insulinolysiini hajoittaa insuliinia koska insuliini ei ubikitinoidu ja ole proteosomaalisesti hajoitettavissa, vaan IDE-kombinoituu proteosomaalisiin osiin ja insuliini säätelee sen avulla proteosomaalista funktiota.- Insulin-degrading enzyme (IDE): A novel heat shock-like ...
https://www.researchgate.net/publication/233789522_Insulin-degrading_enzyme_IDE_A...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.
Artikkeli vuodelta 1983: insulinolyysiksestä https://www.ncbi.nlm.nih.gov/pubmed/?term=insulinolysin
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