Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 21, Pages 3636-3648Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.028654
Keywords
Cyclophilin B; Endoplasmic reticulum stress; Peptidyl prolyl cis-trans isomerase (Pplase); Reactive oxygen species (ROS)
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Funding
- Korea Science and Engineering Foundation [R13-2002-020-02001-0 (2007)]
- Seoul RNBD program [11062]
- Republic of Korea
- NIH [DK42394]
- National Research Foundation of Korea [R13-2002-020-02001-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca2+ leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.
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