ArticleThe Journal of biological chemistry2011
Functional relevance of a novel SlyX motif in non-conventional secretion of insulin-degrading enzyme.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Antibody-Mediated Inhibition of Insulin-Degrading Enzyme Improves Insulin Activity in a Diabetic Mouse Model.Frontiers in immunology · 2022Article
- Secretory Autophagy and Its Relevance in Metabolic and Degenerative Disease.Frontiers in endocrinology · 2020Review
- Insulin-degrading enzyme is not secreted from cultured cells.Scientific reports · 2018Article
- 6-Hydroxydopamine induces secretion of PARK7/DJ-1 via autophagy-based unconventional secretory pathway.Autophagy · 2018Article
- Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Domain architecture of vasohibins required for their chaperone-dependent unconventional extracellular release.Protein science : a publication of the Protein Society · 2017Article
- Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease.Autophagy · 2016Article
- Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.Trends in endocrinology and metabolism: TEM · 2016Review
- Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice.Nature communications · 2015Article
- Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo.The Journal of biological chemistry · 2015Article
- Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.PloS one · 2015Article
- Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-β hydrolysis.European journal of medicinal chemistry · 2014Article
- Unconventional protein secretion: an evolving mechanism.The EMBO journal · 2013Review
- Insulin-degrading enzyme (IDE): a novel heat shock-like protein.The Journal of biological chemistry · 2013Article
- Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes.The Journal of biological chemistry · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin-degrading enzyme (IDE) is a Zn(2+) metalloprotease with a characteristic inverted catalytic motif. IDE is ubiquitously expressed and degrades peptide substrates including insulin, endorphin, and the amyloid-β peptide. Although IDE is mainly expressed in the cytosol, it can also be found on the cell surface and in secreted form in extracellular fluids. As IDE lacks a characteristic signal sequence that targets the protein to the classical secretory pathway, release of the enzyme involves non-conventional mechanisms. However, functional domains of IDE involved in its secretion remain elusive. By bioinformatical, biochemical, and cell biological methods, we identified a novel amino acid motif ((853)EKPPHY(858)) close to the C terminus of IDE and characterized its function in the non-conventional secretion of the protein. Because of its close homology to an amino acid sequence found in bacterial proteins belonging to the SlyX family, we propose to call it the SlyX motif. Mutagenesis revealed that deletion of this motif strongly decreased the release of IDE, whereas deletion of a potential microbody-targeting signal at the extreme C terminus had little effect on secretion. The combined data indicate that the non-conventional secretion of IDE is regulated by the newly identified SlyX motif.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.