Biological roles of peptidylarginine deiminase in the pathogenic mechanisms of keratin deseases : molecular biological approach

肽基精氨酸脱亚胺酶（PAD）是负责将蛋白质结合的精氨酸残基转化为瓜氨酸的酶。最近的研究表明，许多表皮蛋白，包括聚丝蛋白、透明质蛋白和角蛋白，在PAD的作用下被脱亚氨基化，这表明蛋白脱亚氨基化在表皮分化的最后阶段可能起作用。我们在这里报告了一种新的PAD基板过程中发现的脱亚胺蛋白在培养的大鼠表皮角质形成细胞。我们发现，一个70 kD的蛋白定位于细胞核的周边优先脱亚胺离子霉素治疗后，在2 mM的钙的存在下，并与这些细胞中的凋亡事件。此外，发现PAD cDNA转染大鼠表皮角质形成细胞可诱导核蛋白脱亚胺化。这些数据表明，PAD可能作用于70 kD的核蛋白，诱导核板层的解体，并促进细胞凋亡在终末表皮分化。

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 deiminatjon 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, it was discovered that the deimination of nuclear protein could be induced by the 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.