Poet, G. J., Oka, O. B.V. , Van Lith, M., Cao, Z., Robinson, P. J. , Pringle, M. A. , Arnér, E. S.J. and Bulleid, N. (2017) Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER. EMBO Journal, 36(5), pp. 693-702. (doi: 10.15252/embj.201695336) (PMID:28093500) (PMCID:PMC5331760)
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Abstract
Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Van Lith, Dr Marcel and Cao, Dr Zhenbo and Bulleid, Professor Neil and Pringle, Mrs Marie and Robinson, Dr Philip and Oka, Dr Ojore |
Authors: | Poet, G. J., Oka, O. B.V., Van Lith, M., Cao, Z., Robinson, P. J., Pringle, M. A., Arnér, E. S.J., and Bulleid, N. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | EMBO Journal |
Publisher: | EMBO Press |
ISSN: | 0261-4189 |
ISSN (Online): | 1460-2075 |
Published Online: | 16 January 2017 |
Copyright Holders: | Copyright © 2017 The Authors |
First Published: | First published in EMBO Journal 36(5):693-702 |
Publisher Policy: | Reproduced under a Creative Commons License |
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