Proteomic identification of in vivo interactors reveals novel function of skin cornification proteins

Wilbert P Vermeij, Bogdan I Florea, Sheena Isenia, A Alia, Jaap Brouwer, Claude Backendorf

Research output: Contribution to journalArticlepeer-review

Abstract

Protection against injurious external insults and loss of vital fluids is essential for life and is in all organisms, from bacteria to plants and humans, provided by some form of barrier. Members of the small proline-rich (SPRR) protein family are major components of the cornified cell envelope (CE), a structure responsible for the barrier properties of our skin. These proteins are efficient reactive oxygen species (ROS) quenchers involved not only in the establishment of the skin's barrier function but also in cell migration and wound healing. Here, a proteomic analysis of in vivo SPRR-interacting proteins confirmed their function in CE-formation and ROS-quenching and also revealed a novel unexpected role in DNA-binding. Direct in vitro and in vivo evidence proved that the DNA-binding capacity of SPRRs is regulated by the oxidation state of the proteins. At low ROS levels, nuclear SPRR is able to bind DNA and prevent ROS-induced DNA damage. When ROS levels increase, SPRR proteins multimerize and form an effective antioxidant barrier at the cell periphery, possibly to prevent the production or infiltration of ROS. At even higher ROS exposure, DNA-binding is restituted. A molecular model explaining how the intracellular oxidation state of SPRRs likely influences their selective protective function is provided. © 2012 American Chemical Society.
Original languageEnglish
Pages (from-to)3068-3076
Number of pages9
JournalJournal of proteome research
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2012
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • Cornified Envelope Proline-Rich Proteins/chemistry
  • DNA/chemistry
  • DNA Damage
  • Gene Ontology
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide/pharmacology
  • Oxidants/pharmacology
  • Oxidation-Reduction
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Multimerization
  • Protein Transport
  • Proteomics

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