The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 β - Archive ouverte HAL Access content directly
Journal Articles PLoS ONE Year : 2020

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

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Muhammad Saad Khilji
  • Function : Author
Danielle Verstappen
  • Function : Author
Tina Dahlby
  • Function : Author
Celina Pihl
  • Function : Author
Sophie Emilie Bresson
  • Function : Author
Tenna Holgersen Bryde
  • Function : Author
Kristian Klindt
  • Function : Author
Björn Tyrberg
  • Function : Author
Thomas Mandrup-Poulsen
  • Function : Author
Michal Tomasz Marzec
  • Function : Author

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.
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hal-03018741 , version 1 (23-03-2021)

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Muhammad Saad Khilji, Danielle Verstappen, Tina Dahlby, Michala Cecilie Burstein Prause, Celina Pihl, 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), pp.e0222432. ⟨10.1371/journal.pone.0222432⟩. ⟨hal-03018741⟩
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