Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress
| Autor: | Carolyn S. Sevier, Jie Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
genetic structures Cell Survival Peptide binding Saccharomyces cerevisiae macromolecular substances Oxidative phosphorylation medicine.disease_cause Biochemistry Fungal Proteins 03 medical and health sciences chemistry.chemical_compound medicine HSP70 Heat-Shock Proteins Cysteine Molecular Biology chemistry.chemical_classification Reactive oxygen species Endoplasmic reticulum Cell Biology Glutathione Peroxides Cell biology Oxidative Stress 030104 developmental biology chemistry Sulfenic acid Oxidation-Reduction Oxidative stress |
| Zdroj: | Journal of Biological Chemistry. 291:7541-7557 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.694810 |
| Popis: | Redox fluctuations within cells can be detrimental to cell function. To gain insight into how cells normally buffer against redox changes to maintain cell function, we have focused on elucidating the signaling pathways that serve to sense and respond to oxidative redox stress within the endoplasmic reticulum (ER) using yeast as a model system. Previously, we have shown that a cysteine in the molecular chaperone BiP, a Hsp70 molecular chaperone within the ER, is susceptible to oxidation by peroxide during ER-derived oxidative stress, forming a sulfenic acid (−SOH) moiety. Here, we demonstrate that this same conserved BiP cysteine is susceptible also to glutathione modification (−SSG). Glutathionylated BiP is detected both as a consequence of enhanced levels of cellular peroxide and also as a by-product of increased levels of oxidized glutathione (GSSG). Similar to sulfenylation, we observe glutathionylation decouples BiP ATPase and peptide binding activities, turning BiP from an ATP-dependent foldase into an ATP-independent holdase. We show glutathionylation enhances cell proliferation during oxidative stress, which we suggest relates to modified BiP's increased ability to limit polypeptide aggregation. We propose the susceptibility of BiP to modification with glutathione may serve also to prevent irreversible oxidation of BiP by peroxide. |
| Databáze: | OpenAIRE |
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