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

  • Amy E. Ford
  • Kevin A. MoranoEmail author
Part of the Heat Shock Proteins book series (HESP, volume 17)


Signaling through protein cysteine residues to regulate diverse biological processes is widely conserved from bacterial to human cells. Differential cysteine reactivity enables cells to sense and respond to perturbations in the cellular redox environment, which may impact protein structure and activity. This chapter will focus on how redox signaling regulates components of the protein quality control network to mitigate proteotoxic stress caused by redox active compounds. While specifics of redox-based activation of the endoplasmic reticulum unfolded protein response and the cytoplasmic heat shock and oxidative stress responses differ, the presence of regulatory proteins containing reactive cysteines is a common feature. Moreover, several protein chaperones are reversibly regulated via cysteine switches that govern their ability to protect or refold damaged polypeptides. These responses are biologically indispensable, given the propensity of dysregulated cells to produce endogenous reactive oxygen species and the prevalence of thiol-reactive xenobiotics in the external environment.


Chaperone Oxidative stress Proteostasis Reactive oxygen species Redox Signaling 



cysteine-rich domain




endoplasmic reticulum


high molecular weight


heat shock


heat shock protein


heat shock response


low molecular weight


nucleotide binding domain


nucleotide exchange factor


oxidative stress


oxidative stress response


protein disulfide isomerase


protein quality control




reactive oxygen species


sulfenic acid


transcription factor




unfolded protein response



Work in the authors’ laboratory was supported by NIH grant GM127287.


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Authors and Affiliations

  1. 1.Department of Microbiology and Molecular GeneticsUniversity of Texas McGovern Medical School at HoustonHoustonUSA
  2. 2.MD Anderson UT Health Graduate School of Biomedical SciencesHoustonUSA

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