Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

Wang, Jie; Pareja, Kristeen; Kaiser, Chris A.; Sevier, Carolyn S.

doi:10.7554/elife.03496

Cited by 101 publications

(174 citation statements)

References 54 publications

(65 reference statements)

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“…These data imply a capacity for BiP to sense increases in both peroxide and GSSG within the ER lumen. Similar to what we reported previously for sulfenylated BiP (9), glutathionylated BiP shows enhanced holdase activity, which we propose serves to prevent protein aggregation and promote cell survival during stress. By employing BiP alleles with an increased susceptibility to oxidation by glutathione, we observed an enhanced growth rate that correlates with the proportion of oxidized BiP in cells during stress.…”

supporting

confidence: 89%

“…9. CSY318 and CSY693-CSY697 were generated by transformation of CSY214 with pCS757, pCS760, pJW22, pJW23, pJW36, or pJW37, respectively, followed by counter-selection of pCS623 on SMM with 5-fluoroorotic acid.…”

Section: Methodsmentioning

confidence: 99%

“…9. His-tagged BiP ATPase domain proteins (Kar2 residues 48 -428) were induced and purified from BL21 (DE3) pLysS cells.…”

Section: Methodsmentioning

confidence: 99%

“…Chemiluminescent and fluorescent signals were detected using a ChemiDoc MP System (Bio-Rad). DAz-2 samples were processed as described previously (9). CSY316 and CSY319 containing pRS316 were grown to mid-log at 30°C and treated with 5 mM CHP or 10 mM diamide for 15 min prior to harvest.…”

Section: Methodsmentioning

confidence: 99%

“…Oxidation of active site cysteines in the oxidoreductase PDI has been demonstrated to trigger a conformational change that exposes a hydrophobic patch to facilitate high chaperone activity (8). Similarly, oxidation of cysteine(s) in the Hsp70 chaperone BiP can augment BiP activity as a polypeptide holdase (9,10). …”

mentioning

confidence: 99%

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Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress

Wang

Sevier

2016

Journal of Biological Chemistry

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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.Cell homeostasis and numerous vital cell functions rely on the maintenance of a proper intracellular redox balance. Oxidative folding in the endoplasmic reticulum (ER) 2 is one intracellular system that is prone to disruption upon alterations in the redox poise. Insufficient oxidizing capacity in the ER leads to the accumulation of proteins in reduced non-native states (1, 2). Alternatively, an overly oxidizing ER results in cellular toxicity, likely caused in part by the mis-pairing of protein cysteine residues resulting from a decreased capacity to reduce nonnative disulfides (3, 4). Crucial for maintaining a continual flux of folding polypeptides through the ER are the systems that buffer against fluctuations in the ER redox environment.Recently, several proteins have been demonstrated to act as sensors of redox fluctuations in the ER. In a common theme, these proteins sense changes in the ER redox environment and respond with beneficial alterations in their enzymatic activities. The enzyme Ero1 is a major source of oxidizing equivalents in the ER, and Ero1 activity is coupled to the ER redox environment. When the ER balance shifts to overly oxidizing conditions, regulatory cysteine residues in Ero1 become oxidized to disulfides, which decreases Ero1 oxidase activity to help restore redox balance (5-7). In addition, sensors that cope with the potential for protein folding defects have emerged. These redox-dependent chaperones do not directly impact the flux of oxidizing equivalents, like Ero1, but rather are activated to help limit polypeptide aggregation during unfavorable redox conditions. Oxidation of active site cysteines in the oxidoreductase PDI has been demonstrated to...

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supporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

“…9. His-tagged BiP ATPase domain proteins (Kar2 residues 48 -428) were induced and purified from BL21 (DE3) pLysS cells.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress

Wang

Sevier

2016

Journal of Biological Chemistry

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The plant endoplasmic reticulum UPRome: A repository and pathway browser for genes involved in signaling networks linked to the endoplasmic reticulum

et al. 2022

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The endoplasmic reticulum (ER) houses sensors that respond to environmental stress and underly plants' adaptative responses. These sensors transduce signals that lead to changes in nuclear gene expression. The ER to nuclear signaling pathways are primarily attributed to the unfolded protein response (UPR) and are also integrated with a wide range of development, hormone, immune, and stress signaling pathways.Understanding the role of the UPR in signaling network mechanisms that associate with particular phenotypes is crucially important. While UPR-associated genes are the subject of ongoing investigations in a few model plant systems, most remain poorly annotated, hindering the identification of candidates across plant species. This open-source curated database provides a centralized resource of peer reviewed knowledge of ER to nuclear signaling pathways for the plant community. We provide a UPRome interactive viewer for users to navigate through the pathways and to access annotated information. The plant ER UPRome website is located at http:// uprome.tamu.edu. We welcome contributions from the researchers studying the ER UPR to incorporate additional genes into the database through the "contact us" page.

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Thiol-Based Redox Signaling: Impacts on Molecular Chaperones and Cellular Proteostasis

Ford

Morano

2019

Heat Shock Proteins

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Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

Cited by 101 publications

References 54 publications

Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress

Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress

The plant endoplasmic reticulum UPRome: A repository and pathway browser for genes involved in signaling networks linked to the endoplasmic reticulum

Thiol-Based Redox Signaling: Impacts on Molecular Chaperones and Cellular Proteostasis

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