Hydrogen peroxide sensing, signaling and regulation of transcription factors
By H. Marinho, Carla Real, L. Cyrne, Helena Soares, F. Antunes. Redox Biology, 2014
809 citations recorded by the source corpus.
The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/dbaaef1a34d5e289427ad1b45d6d49b060718913
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Citations in the corpus
- Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling (2018, positive): “The redox relay model proposes that thiol peroxidases, in particular Prxs, are the initial recipients of H2O2 and subsequently transfer redox equivalents to the end targets (Reczek and Chandel, 2015; Stöcker et al., 2018).”
- Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress☆ (2017, background): “…at ScienceDirect Redox Biology journal homepage: www.elsevier.com/locate/redox Review article Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress☆ Helmut Siesa,b,⁎ a Institute of Biochemistry and Molecular Biology I, Heinrich Heine…”
- Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction (2015, background): “Other studies on H2O2-mediated signaling are summarized in several reviews [75–77].”
- The Role of Oxidative Stress in Neurodegenerative Diseases (2015, background): “Since PRX are abundant in eukaryotic cells, constitute approximately more than 1% of cellular proteins, and show high reactivity, PRX are responsible for the reduction of up to 90% of mitochondrial H2O2 and almost 100% of cytoplasmic H2O2 [48-51].”