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Journal of Histochemistry and Cytochemistry, Vol. 46, 1303-1310, November 1998, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

Deimination of 70-kD Nuclear Protein During Epidermal Apoptotic Events In Vitro

Masayuki Mizoguchia, Motomu Manabea, Yasushi Kawamuraa, Yukiko Kondoa, Kazumi Ishidohb, Eiki Kominamib, Kazutaka Watanabec, Hiroaki Asagad, Tatsuo Senshud, and Hideoki Ogawaa
a Departments of Dermatology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
b Biochemistry, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
c Juntendo University School of Medicine, and Departments of Experimental Biology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
d Cell Chemistry, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Correspondence to: Motomu Manabe, Dept. of Dermatology, Juntendo University School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo 113, Japan..

Peptidylarginine deiminase (PAD) is the enzyme responsible for converting protein-bound arginine residues to citrulline. It has recently been shown that a number of epidermal proteins, including filaggrin, trichohyalin, and keratins, are deiminated by the action of PAD, suggesting a possible role for protein deimination during the final stages of epidermal differentiation. We report here a novel PAD substrate found during the course of identifying deiminated proteins in cultured rat epidermal keratinocytes. We found that a 70-kD protein localized to the periphery of the nucleus was preferentially deiminated after ionomycin treatment in the presence of 2 mM calcium and was associated with apoptotic events in these cells. Furthermore, we discovered that the deimination of nuclear protein could be induced by transfection of a PAD cDNA into rat epidermal keratinocytes. These data suggest that PAD may act on the 70-kD nuclear protein to induce disassembly of the nuclear lamina and promote apoptosis during terminal epidermal differentiation. (J Histochem Cytochem 46:1303–1309, 1998)

Key Words: nuclear protein, peptidylarginine deiminase, epidermal differentiation


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