WFRF:(Mandrup Poulsen T)
Sökning: WFRF:(Mandrup Poulsen T) > (2020) > The inducible β5i p...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04658naa a2200841 4500 | |
| 001 | oai:gup.ub.gu.se/297807 | |
| 003 | SwePub | |
| 008 | 240528s2020 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://gup.ub.gu.se/publication/2978072 URI |
| 024 | 7 | a https://doi.org/10.1152/AJPENDO.00372.20192 DOI |
| 040 | a (SwePub)gu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Khilji, M. S.4 aut |
| 245 | 1 0 | a The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94-deficient β-cells and is overexpressed in type 2 diabetes pancreatic islets |
| 264 | 1 | c 2020 |
| 520 | a Proinsulin is a misfolding-prone protein, and its efficient breakdown is critical when β-cells are confronted with high-insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone glucoseregulated protein 94 (GRP94) causes impaired proinsulin handling and defective insulin secretion associated with a compensated endoplasmic reticulum stress response. Taking advantage of this model of restricted folding capacity, we investigated the role of different proteasomes in proinsulin degradation, reasoning that insulin secretory dynamics require an inducible protein degradation system. We show that the expression of only one enzymatically active proteasome subunit, namely, the inducible β5i-subunit, was increased in GRP94 CRISPR/Cas9 knockout (KO) cells. Additionally, the level of β5i-containing intermediate proteasomes was significantly increased in these cells, as was β5i-related chymotrypsin-like activity. Moreover, proinsulin levels were restored in GRP94 KO upon β5i small interfering RNA-mediated knockdown. Finally, the fraction of β-cells expressing the β5i subunit is increased in human islets from type 2 diabetes patients. We conclude that β5i is an inducible proteasome subunit dedicated to the degradation of mishandled proinsulin. Copyright © 2020 the American Physiological Society. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng |
| 653 | a 5i | |
| 653 | a GRP94 | |
| 653 | a Proinsulin degradation | |
| 653 | a Proteasome | |
| 653 | a Restoration of proinsulin | |
| 653 | a chymotrypsin | |
| 653 | a glucose regulated protein 94 | |
| 653 | a inducible beta5i proteasome subunit | |
| 653 | a insulin | |
| 653 | a proinsulin | |
| 653 | a unclassified drug | |
| 653 | a adult | |
| 653 | a Article | |
| 653 | a clinical article | |
| 653 | a controlled study | |
| 653 | a endoplasmic reticulum | |
| 653 | a female | |
| 653 | a gene expression | |
| 653 | a human | |
| 653 | a human tissue | |
| 653 | a INS-1 cell line | |
| 653 | a insulin release | |
| 653 | a middle aged | |
| 653 | a mRNA expression level | |
| 653 | a non insulin dependent diabetes mellitus | |
| 653 | a pancreas islet beta cell | |
| 653 | a priority journal | |
| 653 | a protein degradation | |
| 653 | a protein expression | |
| 653 | a protein folding | |
| 653 | a single cell RNA seq | |
| 700 | 1 | a Bresson, S. E.4 aut |
| 700 | 1 | a Verstappen, D.4 aut |
| 700 | 1 | a Pihl, C.4 aut |
| 700 | 1 | a Andersen, P. A. K.4 aut |
| 700 | 1 | a Agergaard, J. B.4 aut |
| 700 | 1 | a Dahlby, T.4 aut |
| 700 | 1 | a Bryde, T. H.4 aut |
| 700 | 1 | a Klindt, K.4 aut |
| 700 | 1 | a Nielsen, C. K.4 aut |
| 700 | 1 | a Walentinsson, A.4 aut |
| 700 | 1 | a Zivkovic, D.4 aut |
| 700 | 1 | a Bousquet, M. P.4 aut |
| 700 | 1 | a Tyrberg, Björnu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut |
| 700 | 1 | a Richardso, S. J.4 aut |
| 700 | 1 | a Morga, N. G.4 aut |
| 700 | 1 | a Mandrup-Poulsen, T.4 aut |
| 700 | 1 | a Marzec, M. T.4 aut |
| 710 | 2 | a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi4 org |
| 773 | 0 | t American Journal of Physiology - Endocrinology and Metabolismg 318:6q 318:6x 0193-1849 |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/297807 |
| 856 | 4 8 | u https://doi.org/10.1152/AJPENDO.00372.2019 |
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