IKKα regulates human keratinocyte migration through surveillance of the redox environment

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 IKKa promotes migration through dynamic interactions with the EGF promoter depending on the redox state within cells.

Original languageEnglish (US)
Pages (from-to)975-988
Number of pages14
JournalJournal of Cell Science
Volume130
Issue number5
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • EGF
  • HO
  • HEK001
  • Hydrogen peroxide
  • IKKα
  • Keratinocytes
  • Migration
  • Nuclear de-repression
  • Oxidation
  • Reactive oxygen species
  • Sulfenylation
  • Wound healing
  • Wound repair

ASJC Scopus subject areas

  • Cell Biology

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