Abstract
The existence of citrulline in proteins was first described in the skin. In a paper published in Nature in 1958, George Rogers reported citrulline in a protein of hair follicles (Rogers and Simmonds 1958). Twenty-eight years later, Rothnagel and Rogers purified and characterised the corresponding protein and called it trichohyalin (Rothnagel and Rogers 1986). Since then, deiminated proteins have been detected in almost all cells, tissues and organs. The enzymes responsible for this posttranslational modification, the peptidylarginine deiminases (PADs), also known as protein-arginine deiminases, are becoming increasingly well known. Five types of PADs have been identified in humans and other mammals, the PAD1, 2, 3, 4 (also known as PAD5), and 6 (Vossenaar et al. 2003; Chavanas et al. 2004; Balandraud et al. 2005). They are encoded by five paralogous genes clustered on chromosome 1p35-36 and named PADI1, 2, 3, 4 and 6 (Vossenaar et al. 2003; Chavanas et al. 2004). The importance of PADs in many cellular processes is now recognised (Klose and Zhang 2007; Li et al. 2010; Struyf et al. 2009; Esposito et al. 2007) and PADs have been involved in the pathogenesis of autoimmune diseases, e.g. rheumatoid arthritis (Klareskog et al. 2008; Sebbag et al. 2004), multiple sclerosis (Harauz and Musse 2007; Kim et al. 2003) and cancer (Slack et al. 2011a), that are described in more detail in other chapters of this book. Here, we report on the location of PADs expressed in skin; the mechanisms involved in the regulation of their expression and activity in keratinocytes, their skin targets and physiological roles; and, finally, their possible contribution to skin diseases.
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Acknowledgements
We are indebted to all members of HT and GS laboratories involved in PAD research in the past and/or in the present time. HT laboratory is supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan. Investigation of PADs in the GS laboratory has been or is supported by the CNRS, the University of Toulouse III, the INSERM, the French Society for Dermatology (SFD), the Society for Dermatological Research (SRD) and Pierre Fabre Dermo-Cosmétique.
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Takahara, H., Serre, G., Simon, M. (2014). Deimination in Skin and Regulation of Peptidylarginine Deiminase Expression in Keratinocytes. In: Nicholas, A., Bhattacharya, S. (eds) Protein Deimination in Human Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8317-5_7
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