Deimination is regulated at multiple levels including auto-deimination of peptidylarginine deiminases.

Cellular and Molecular Life Sciences : CMLS
Marie-Claire MéchinMichel Simon

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.

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Citations

Oct 31, 2012·Journal of Periodontology·Ceilidh MarchantP Mark Bartold
Oct 29, 2013·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Akira ShimizuHidenari Takahara
Aug 15, 2013·Critical Reviews in Oncology/hematology·Michelino Di RosaLucia Malaguarnera
Sep 23, 2018·Molecular Carcinogenesis·Chunyan LiuXiaotian Chang
Jan 19, 2020·International Journal of Molecular Sciences·Marie-Claire MéchinMichel Simon
May 15, 2018·Experimental Dermatology·Laura CauMichel Simon
Apr 29, 2020·Nature Reviews. Rheumatology·Ashley M CurranErika Darrah
Jun 14, 2020·Annals of the Rheumatic Diseases·Madeleine JenningKarl Skriner
Nov 25, 2020·International Journal of Molecular Sciences·Julie BriotMarie-Claire Méchin
Apr 29, 2021·Antioxidants & Redox Signaling·Maria Isabel Trejo-ZambranoFelipe Andrade

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