PUBLICATION
IKKα regulates human keratinocyte migration through surveillance of the redox environment
- Authors
- Lisse, T.S., Rieger, S.
- ID
- ZDB-PUB-170805-20
- Date
- 2017
- Source
- Journal of Cell Science 130: 975-988 (Journal)
- Registered Authors
- Rieger, Sandra
- Keywords
- EGF, H2O2, HEK001, Hydrogen peroxide, IKKα, Keratinocytes, Migration, Nuclear de-repression, Oxidation, Reactive oxygen species, Sulfenylation, Wound healing, Wound repair
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- Cell Movement*
- Cysteine/metabolism
- Epidermal Growth Factor/genetics
- Humans
- Hydrogen Peroxide
- I-kappa B Kinase/chemistry
- I-kappa B Kinase/metabolism*
- Keratinocytes/cytology*
- Keratinocytes/metabolism*
- Oxidation-Reduction
- Promoter Regions, Genetic/genetics
- Protein Processing, Post-Translational/drug effects
- Signal Transduction/drug effects
- Wound Healing/drug effects
- Zebrafish
- PubMed
- 28122935 Full text @ J. Cell Sci.
Citation
Lisse, T.S., Rieger, S. (2017) IKKα regulates human keratinocyte migration through surveillance of the redox environment. Journal of Cell Science. 130:975-988.
Abstract
Although the functions of H2O2 in epidermal wound repair are conserved throughout evolution, the underlying signaling mechanisms are largely unknown. In this study we used human keratinocytes (HEK001) to investigate H2O2-dependent wound repair mechanisms. Scratch wounding led to H2O2 production in two or three cell layers at the wound margin within ∼30 min and subsequent cysteine modification of proteins via sulfenylation. Intriguingly, exogenous H2O2 treatment resulted in preferential sulfenylation of keratinocytes that adopted a migratory phenotype and detached from neighboring cells, suggesting that one of the primary functions of H2O2 is to stimulate signaling factors involved in cell migration. Based on previous findings that revealed epidermal growth factor receptor (EGFR) involvement in H2O2-dependent cell migration, we analyzed oxidation of a candidate upstream target, the inhibitor of κB kinase α (IKKα; encoded by CHUK), as a mechanism of action. We show that IKKα is sulfenylated at a conserved cysteine residue in the kinase domain, which correlates with de-repression of EGF promoter activity and increased EGF expression. Thus, this indicates that IKKα promotes migration through dynamic interactions with the EGF promoter depending on the redox state within cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping