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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

21 Citaten (Scopus)


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.
Originele taal-2Engels
Pagina's (van-tot)3068-3076
Aantal pagina's9
TijdschriftJournal of proteome research
Nummer van het tijdschrift6
StatusGepubliceerd - 1 jun. 2012
Extern gepubliceerdJa


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