Quantitative phosphoproteomics identifies filaggrin and other targets of ionizing radiation in a human skin model

: Our objective here was to perform a quantitative phosphoproteomic study on a reconstituted human skin tissue to identify low‐ and high‐dose ionizing radiation‐dependent signalling in a complex three‐dimensional setting. Application of an isobaric labelling strategy using sham and three radiation...

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Bibliographic Details
Published in:	Experimental dermatology Vol. 21; no. 5; pp. 352 - 357
Main Authors:	Yang, Feng, Waters, Katrina M., Webb-Robertson, Bobbie-Jo, Sowa, Marianne B., von Neubeck, Claere, Aldrich, Josh T., Meng Markillie, Lye, Wirgau, Rachel M., Gritsenko, Marina A., Zhao, Rui, Camp II, David G., Smith, Richard D., Stenoien, David L.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-05-2012 Blackwell
Subjects:	BASIC BIOLOGICAL SCIENCES Biological and medical sciences BIOLOGICAL RADIATION EFFECTS Dermatology Desmogleins - metabolism Desmoplakins - metabolism Dose-Response Relationship, Radiation Environmental Molecular Sciences Laboratory EPITHELIUM Humans Intermediate Filament Proteins - metabolism ionizing radiation IONIZING RADIATIONS KERATIN Keratins - metabolism LOW DOSE IRRADIATION Medical sciences PEPTIDES Phosphopeptides - metabolism Phosphoproteins - metabolism PHOSPHORYLATION Phosphorylation - radiation effects Plakophilins - metabolism PROTEINS Proteomics RADIATION DOSES Radiation, Ionizing RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS Signal Transduction - radiation effects SKIN Skin - metabolism Skin - radiation effects Human Phosphorylation Dermatology Models Skin ionizing radiation Quantitative analysis
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Summary:	: Our objective here was to perform a quantitative phosphoproteomic study on a reconstituted human skin tissue to identify low‐ and high‐dose ionizing radiation‐dependent signalling in a complex three‐dimensional setting. Application of an isobaric labelling strategy using sham and three radiation doses (3, 10, 200 cGy) resulted in the identification of 1052 unique phosphopeptides. Statistical analyses identified 176 phosphopeptides showing significant changes in response to radiation and radiation dose. Proteins responsible for maintaining skin structural integrity including keratins and desmosomal proteins (desmoglein, desmoplakin, plakophilin 1, 2 and 3) had altered phosphorylation levels following exposure to both low and high doses of radiation. Altered phosphorylation of multiple sites in profilaggrin linker domains coincided with altered profilaggrin processing suggesting a role for linker phosphorylation in human profilaggrin regulation. These studies demonstrate that the reconstituted human skin system undergoes a coordinated response to both low and high doses of ionizing radiation involving multiple layers of the stratified epithelium that serve to maintain tissue integrity and mitigate effects of radiation exposure.
Bibliography:	ark:/67375/WNG-9N7KVHLF-G istex:884C202614520DDCC9F36C2D2B887ED7417A3924 ArticleID:EXD1470 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 USDOE AC05-76RL01830 PNNL-SA-79030
ISSN:	0906-6705 1600-0625
DOI:	10.1111/j.1600-0625.2012.01470.x