Deimination of 70-kD nuclear protein during epidermal apoptotic events in vitro.
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.
Department of Dermatology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
M
M
Mizoguchi
M
M
Manabe
Y
Y
Kawamura
Y
Y
Kondo
K
K
Ishidoh
E
E
Kominami
K
K
Watanabe
H
H
Asaga
T
T
Senshu
H
H
Ogawa
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D019084:Fluorescent Antibody Technique, Indirect; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D051381:Rats; D014162:Transfection
D009687:Nuclear Proteins; D015759:Ionomycin; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases