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

肽基精氨酸脱亚胺酶在角蛋白疾病致病机制中的生物学作用：分子生物学方法

• 批准号: 09670896
• 负责人: MANABE Motomu
• 金额: $ 1.79万
• 依托单位: AKITA UNIVERSITY (1998)Juntendo University (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670896/
• 关键词: peptidylarginine deiminase; keratins; apoptosis; 表皮分化; peptidylarginine deiminase

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.

肽基精氨酸脱亚胺酶(PAD)是一种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，包括微丝蛋白、毛发纤维蛋白和角蛋白都被PAD作用去亚胺，这表明蛋白质去亚胺可能在表皮分化的最后阶段起作用。我们报道了一种新的PAD底物，在鉴定培养的大鼠表皮角质形成细胞中去亚胺蛋白的过程中发现了这种底物。我们发现，在2 mM钙离子存在下，离子霉素处理后，定位于细胞核外围的70kD蛋白优先去亚胺，并与这些细胞的凋亡事件有关。此外，我们还发现，将pAD基因导入大鼠表皮角质形成细胞，可以诱导核蛋白的脱亚基。这些结果表明，PAD可能作用于70kD的核蛋白，诱导核层的解体，促进表皮终末分化过程中的细胞凋亡。

项目成果

Mizoguchi M et al.: "Deimination of 70 kD Nuclear Protein During Epidermal Apoptotic Events In Vitro." J.Histochem.Cytochem.46. 1-7 (1998)

Mizoguchi M 等人：“体外表皮细胞凋亡事件期间 70 kD 核蛋白的去亚胺化”。

Mizoguchi M et al.: "Deimination of 70 kD Nuclear Protein During Epidermal Apoptotic Events Vitro." J.Histochem.Cytochem.46. 1-7 (1998)

Mizoguchi M 等人：“体外表皮细胞凋亡事件期间 70 kD 核蛋白的去亚胺化”。