title: Deimination is regulated at multiple levels including auto-deimination of peptidylarginine deiminases.
abstract: Peptidylarginine deiminases (PADs) catalyze deimination, converting arginyl to citrullyl residues. Only three PAD isotypes are detected in the epidermis where they play a crucial role, targeting filaggrin, a key actor for the tissue hydration and barrier functions. Their expression and activation depends on the keratinocyte differentiation state. To investigate this regulation, we used primary keratinocytes induced to differentiate either by increasing cell-density or by treatment with vitamin D. High cell-density increased PAD1 and 3, but not PAD2, at the mRNA and protein levels, and up-regulated protein deimination. By contrast, vitamin D increased PAD1-3 mRNA amounts, with distinct kinetics, but neither the proteins nor the deimination rate. Furthermore, auto-deimination was shown to decrease PAD activity, increasing the distances between the four major amino acids of the active site. In summary, deimination can be regulated at multiple levels: transcription of the PADI genes, translation of the corresponding mRNAs, and auto-deimination of PADs.
authors.affiliation: CNRS-University of Toulouse III, UMR5165, Institut Fédératif de Recherche 150 (INSERM-CNRS-Université paul Sabatier-Centre Hospitalier Universitaire de Toulouse), CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse Cedex 9, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Méchin
authors.forename: Fanny
authors.initials: F
authors.lastname: Coudane
authors.forename: Véronique
authors.initials: V
authors.lastname: Adoue
authors.forename: Jacques
authors.initials: J
authors.lastname: Arnaud
authors.forename: Hélène
authors.initials: H
authors.lastname: Duplan
authors.forename: Marie
authors.initials: M
authors.lastname: Charveron
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schmitt
authors.forename: Hidenari
authors.initials: H
authors.lastname: Takahara
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Michel
authors.initials: M
authors.lastname: Simon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D007097:Imines / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007097:Imines; D007381:Intermediate Filament Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014815:Vitamins; D014807:Vitamin D; D002956:Citrulline; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases