Hydrogen peroxide sensing, signaling and regulation of transcription factors
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 complexit...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231714000457 |
| _version_ | 1818146474468311040 |
|---|---|
| author | H. Susana Marinho Carla Real Luísa Cyrne Helena Soares Fernando Antunes |
| author_facet | H. Susana Marinho Carla Real Luísa Cyrne Helena Soares Fernando Antunes |
| author_sort | H. Susana Marinho |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T12:19:56Z |
| format | Article |
| id | doaj.art-0b7d07296abd4ec2ac7befa27d30f8bd |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-11T12:19:56Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-0b7d07296abd4ec2ac7befa27d30f8bd2022-12-22T01:07:34ZengElsevierRedox Biology2213-23172014-01-012C53556210.1016/j.redox.2014.02.006Hydrogen peroxide sensing, signaling and regulation of transcription factorsH. Susana Marinho0Carla Real1Luísa Cyrne2Helena Soares3Fernando Antunes4Departamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, PortugalDepartamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, PortugalDepartamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, PortugalDepartamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, PortugalDepartamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, PortugalThe 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.http://www.sciencedirect.com/science/article/pii/S2213231714000457Redox signalingLocalized H2O2 concentrationsRate constantsThiol reactivityCytosol-nuclear trafficDNA binding and transactivation |
| spellingShingle | H. Susana Marinho Carla Real Luísa Cyrne Helena Soares Fernando Antunes Hydrogen peroxide sensing, signaling and regulation of transcription factors Redox Biology Redox signaling Localized H2O2 concentrations Rate constants Thiol reactivity Cytosol-nuclear traffic DNA binding and transactivation |
| title | Hydrogen peroxide sensing, signaling and regulation of transcription factors |
| title_full | Hydrogen peroxide sensing, signaling and regulation of transcription factors |
| title_fullStr | Hydrogen peroxide sensing, signaling and regulation of transcription factors |
| title_full_unstemmed | Hydrogen peroxide sensing, signaling and regulation of transcription factors |
| title_short | Hydrogen peroxide sensing, signaling and regulation of transcription factors |
| title_sort | hydrogen peroxide sensing signaling and regulation of transcription factors |
| topic | Redox signaling Localized H2O2 concentrations Rate constants Thiol reactivity Cytosol-nuclear traffic DNA binding and transactivation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231714000457 |
| work_keys_str_mv | AT hsusanamarinho hydrogenperoxidesensingsignalingandregulationoftranscriptionfactors AT carlareal hydrogenperoxidesensingsignalingandregulationoftranscriptionfactors AT luisacyrne hydrogenperoxidesensingsignalingandregulationoftranscriptionfactors AT helenasoares hydrogenperoxidesensingsignalingandregulationoftranscriptionfactors AT fernandoantunes hydrogenperoxidesensingsignalingandregulationoftranscriptionfactors |