title: Proteomic identification of in vivo interactors reveals novel function of skin cornification proteins.
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.
authors.affiliation: Department of Molecular Genetics, ‡Bio-Organic Synthesis, and §Solid State NMR, Leiden Institute of Chemistry, Faculty of Science, Leiden University , P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Wilbert P
authors.initials: WP
authors.lastname: Vermeij
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Florea
authors.forename: Sheena
authors.initials: S
authors.lastname: Isenia
authors.forename: A
authors.initials: A
authors.lastname: Alia
authors.forename: Jaap
authors.initials: J
authors.lastname: Brouwer
authors.forename: Claude
authors.initials: C
authors.lastname: Backendorf
mesh_terms: D000595:Amino Acid Sequence; D055233:Cornified Envelope Proline-Rich Proteins / Q000737:chemistry / Q000502:physiology*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D063990:Gene Ontology; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D021381:Protein Transport; D040901:Proteomics
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D016877:Oxidants; D004247:DNA; D006861:Hydrogen Peroxide