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Functional Significance of Protein Deimination during the Cornification of Epidermis

表皮角化过程中蛋白质脱亚胺的功能意义

基本信息

批准号：
07680703
负责人：
SENSHU Tatsuo
金额：
$ 1.22万
依托单位：
Tokyo Metropolitan Institute of Gerontology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

We previously reported the presence of deiminated keratins and filaggrin in rat epidermis (J.Invest. Dermtol. 105,163-69 (1995) ; supported by Grant-in-Aide 06833012). Here we performed identification of the major deiminated keratin molecule and cloning of peptidylarginine deiminase (PAD) cDNAs. We also conducted comparative studies of protein deimination using various experimental systems.1. Major deiminated proteins in human and mouse epidermis were identified to be partially degraded and disulfide-cross-linked keratin K1 in the cornified layr suggesting the possible role of protein deimination in modulating the interaction of K1 with its partner keratin K10, pre-existent keratins K5/K14 network or keratin-associated proteins.2. Three PAD clones were isolated from a cDNA library of immortalized newbom rat kerationcytes that had been induced to express PAD with retinoic acid. One of them closely resembled skeletal muscle PAD cDNA previously obtained in our laboratory. The other two appeared to be novel cDNAs encoding PADs. Further research is in progress to see if either of them encodes PAD expressed in the epidermis.3. Deimination of keratins and filaggrin in mouse epidermis was found to increase markedly during postnatal few hours. Cultivation of late prenatal embryonic skin suggested that exposure to air is required for normal deimination of these epidermal proteins. Comparative studies using human, rat, mouse, and guine a pig showed significant species differences in filaggrin deimination.

我们先前报道了大鼠表皮中存在脱亚胺角蛋白和聚丝蛋白（J.Invest. Dermtol。105，163 -69（1995）;由Grant-in-Aide 06833012支持）。在这里，我们进行了鉴定的主要脱亚胺角蛋白分子和肽基精氨酸脱亚胺酶（PAD）的cDNA克隆。我们还使用各种实验系统进行了蛋白质脱亚胺的比较研究。人和小鼠表皮中主要的脱亚氨基蛋白被鉴定为部分降解，并且在表皮层中二硫键交联角蛋白K1，这表明蛋白脱亚氨基在调节K1与其伴侣角蛋白K10、预先存在的角蛋白K5/K14网络或角蛋白相关蛋白的相互作用中可能起作用.从用维甲酸诱导表达PAD的永生化新生大鼠角朊细胞的cDNA文库中分离到三个PAD克隆。其中一个与我们实验室先前获得的骨骼肌PAD cDNA非常相似。另外两个似乎是编码PAD的新cDNA。进一步的研究正在进行中，以确定它们是否编码在表皮中表达的PAD。小鼠表皮角蛋白和丝聚蛋白的脱亚氨基化在出生后数小时内显著增加。培养后期产前胚胎皮肤表明，暴露于空气中是需要这些表皮蛋白的正常脱亚胺。使用人、大鼠、小鼠和豚鼠进行的比较研究表明，聚丝蛋白脱亚氨基存在显著的物种差异。