The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β

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The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β. / Khilji, Muhammad Saad; Verstappen, Danielle; Dahlby, Tina; Prause, Michala Cecilie Burstein; Pihl, Celina ; Bresson, Sophie Emilie; Bryde, Tenna Holgersen; Andersen, Phillip Alexander Keller; Klindt, Kristian ; Zivkovic, Dusan; Bousquet-Dubouch, Marie Pierre; Tyrberg, Björn; Mandrup-Poulsen, Thomas; Marzec, Michal Tomasz.

In: PLoS ONE, Vol. 15, No. 2, e0222432, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Khilji, MS, Verstappen, D, Dahlby, T, Prause, MCB, Pihl, C, Bresson, SE, Bryde, TH, Andersen, PAK, Klindt, K, Zivkovic, D, Bousquet-Dubouch, MP, Tyrberg, B, Mandrup-Poulsen, T & Marzec, MT 2020, 'The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β', PLoS ONE, vol. 15, no. 2, e0222432. https://doi.org/10.1371/journal.pone.0222432

APA

Khilji, M. S., Verstappen, D., Dahlby, T., Prause, M. C. B., Pihl, C., Bresson, S. E., ... Marzec, M. T. (2020). The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β. PLoS ONE, 15(2), [e0222432]. https://doi.org/10.1371/journal.pone.0222432

Vancouver

Khilji MS, Verstappen D, Dahlby T, Prause MCB, Pihl C, Bresson SE et al. The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β. PLoS ONE. 2020;15(2). e0222432. https://doi.org/10.1371/journal.pone.0222432

Author

Khilji, Muhammad Saad ; Verstappen, Danielle ; Dahlby, Tina ; Prause, Michala Cecilie Burstein ; Pihl, Celina ; Bresson, Sophie Emilie ; Bryde, Tenna Holgersen ; Andersen, Phillip Alexander Keller ; Klindt, Kristian ; Zivkovic, Dusan ; Bousquet-Dubouch, Marie Pierre ; Tyrberg, Björn ; Mandrup-Poulsen, Thomas ; Marzec, Michal Tomasz. / The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β. In: PLoS ONE. 2020 ; Vol. 15, No. 2.

Bibtex

@article{2982119a65af45e0ae16b04612438b68,
title = "The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β",
abstract = "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 β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β 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 β5i 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-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.",
author = "Khilji, {Muhammad Saad} and Danielle Verstappen and Tina Dahlby and Prause, {Michala Cecilie Burstein} and Celina Pihl and Bresson, {Sophie Emilie} and Bryde, {Tenna Holgersen} and Andersen, {Phillip Alexander Keller} and Kristian Klindt and Dusan Zivkovic and Bousquet-Dubouch, {Marie Pierre} and Bj{\"o}rn Tyrberg and Thomas Mandrup-Poulsen and Marzec, {Michal Tomasz}",
year = "2020",
doi = "10.1371/journal.pone.0222432",
language = "English",
volume = "15",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β

AU - Khilji, Muhammad Saad

AU - Verstappen, Danielle

AU - Dahlby, Tina

AU - Prause, Michala Cecilie Burstein

AU - Pihl, Celina

AU - Bresson, Sophie Emilie

AU - Bryde, Tenna Holgersen

AU - Andersen, Phillip Alexander Keller

AU - Klindt, Kristian

AU - Zivkovic, Dusan

AU - Bousquet-Dubouch, Marie Pierre

AU - Tyrberg, Björn

AU - Mandrup-Poulsen, Thomas

AU - Marzec, Michal Tomasz

PY - 2020

Y1 - 2020

N2 - 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 β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β 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 β5i 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-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.

AB - 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 β cells, as this might facilitate autoantigen presentation by β cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in β 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 β5i 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-1β stimulating proinsulin biosynthesis. These findings suggest that the β cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.

U2 - 10.1371/journal.pone.0222432

DO - 10.1371/journal.pone.0222432

M3 - Journal article

C2 - 32053590

AN - SCOPUS:85079337384

VL - 15

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 2

M1 - e0222432

ER -

ID: 238370888