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The intermediate pr...
The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 beta
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-02-13
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Public Library of Science (PLoS),2020
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/294011
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https://gup.ub.gu.se/publication/294011URI
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https://doi.org/10.1371/journal.pone.0222432DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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A central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic beta cells, as this might facilitate autoantigen presentation by beta cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in beta cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes. We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the beta 5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by low concentrations of IL-1 beta stimulating proinsulin biosynthesis. These findings suggest that the beta cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.
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Verstappen, D.
(author)
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Dahlby, T.
(author)
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Prause, M. C. B.
(author)
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Pihl, C.
(author)
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Bresson, S. E.
(author)
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Bryde, T. H.
(author)
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Andersen, P. A. K.
(author)
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Klindt, K.
(author)
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Zivkovic, D.
(author)
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Bousquet-Dubouch, M. P.
(author)
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Tyrberg, BjörnGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
(author)
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Mandrup-Poulsen, T.
(author)
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Marzec, Michal Tomasz
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi
(creator_code:org_t)
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In:PLoS ONE: Public Library of Science (PLoS)15:21932-6203
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Khilji, M. S.
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Verstappen, D.
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Dahlby, T.
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Prause, M. C. B.
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Pihl, C.
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Bresson, S. E.
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Bryde, T. H.
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Andersen, P. A. ...
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Klindt, K.
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Zivkovic, D.
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Bousquet-Dubouch ...
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Tyrberg, Björn
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Mandrup-Poulsen, ...
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Marzec, Michal T ...
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- MEDICAL AND HEALTH SCIENCES
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PLoS ONE
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University of Gothenburg