Deimination is regulated at multiple levels including auto-deimination of peptidylarginine deiminases.
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.
Méchin
Marie-Claire
MC
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.
Coudane
Fanny
F
Adoue
Véronique
V
Arnaud
Jacques
J
Duplan
Hélène
H
Charveron
Marie
M
Schmitt
Anne-Marie
AM
Takahara
Hidenari
H
Serre
Guy
G
Simon
Michel
M
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
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