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Scientific article
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English

Cyclosporine A-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation

Published inPloS one, vol. 5, no. 9
Publication date2010
Abstract

Peptidyl-prolyl cis/trans isomerases (PPIs) catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER)-resident members of the PPI family in protein folding, quality control or disposal in the living cell. Here we report that the immunosuppressive drug cyclosporine A (CsA) selectively inhibits the degradation of a subset of misfolded proteins generated in the ER. We identify cyclophilin B (CyPB) as the ER-resident target of CsA that catalytically enhances disposal from the ER of ERAD-L(S) substrates containing cis proline residues. Our manuscript presents the first evidence for enzymatic involvement of a PPI in protein quality control in the ER of living cells.

Keywords
  • Cyclophilins/chemistry/*metabolism
  • Cyclosporine/*pharmacology
  • Down-Regulation
  • Endoplasmic Reticulum/chemistry/drug effects/*enzymology
  • HeLa Cells
  • Humans
  • Protein Folding
Citation (ISO format)
BERNASCONI, Riccardo et al. Cyclosporine A-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation. In: PloS one, 2010, vol. 5, n° 9. doi: 10.1371/journal.pone.0013008
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Article (Published version)
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ISSN of the journal1932-6203
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