Cyclosporine A-Sensitive, Cyclophilin B-Dependent Endoplasmic Reticulum-Associated Degradation

被引：41

作者：

Bernasconi, Riccardo ^{[1
]}

Solda, Tatiana ^{[1
]}

Galli, Carmela ^{[1
]}

Pertel, Thomas ^{[1
,2
]}

Luban, Jeremy ^{[1
,2
]}

Molinari, Maurizio ^{[1
,3
]}

机构：

[1] Inst Res Biomed, Bellinzona, Switzerland

[2] Univ Geneva, Dept Microbiol & Mol Med, Geneva, Switzerland

[3] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland

来源：

PLOS ONE | 2010年 / 5卷 / 09期

基金：

瑞士国家科学基金会;

关键词：

UBIQUITIN LIGASE COMPLEX; QUALITY-CONTROL; MISFOLDED GLYCOPROTEINS; CA2+ HOMEOSTASIS; ER; RECOGNITION; PROTEASOME; SECRETION; ISOMERASE; VARIANTS;

D O I：

10.1371/journal.pone.0013008

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

共 36 条

[1] Development of the proteasome inhihitor Veleade™ (Bortezomib) [J].