Wang Fengrong, Zieman Abigail, Coulombe Pierre A
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA; Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Methods Enzymol. 2016;568:303-50. doi: 10.1016/bs.mie.2015.09.032. Epub 2015 Nov 19.
Keratins comprise the type I and type II intermediate filament-forming proteins and occur primarily in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Keratins serve multiple homeostatic and stress-enhanced mechanical and nonmechanical functions in epithelia, including the maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications as well as keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility and/or altered tissue homeostasis. Moreover, keratin mutation or misregulation represents risk factors or genetic modifiers for several acute and chronic diseases. This chapter focuses on keratins that are expressed in skin epithelia, and details a number of basic protocols and assays that have proven useful for analyses being carried out in skin.
角蛋白由I型和II型中间丝形成蛋白组成，主要存在于上皮细胞中。它们由54个进化保守基因（28个I型，26个II型）编码，并以成对且依赖于组织类型、分化和环境的方式受到调控。角蛋白在上皮细胞中发挥多种稳态和应激增强的机械及非机械功能，包括维持细胞完整性、调节细胞生长和迁移以及防止细胞凋亡。这些功能受到翻译后修饰以及角蛋白相关蛋白的严格调控。角蛋白编码序列的遗传决定改变是高外显率和罕见疾病的基础，其病理生理学反映了细胞脆弱性和/或组织稳态改变。此外，角蛋白突变或调控异常是多种急性和慢性疾病的危险因素或遗传修饰因子。本章重点介绍在皮肤上皮中表达的角蛋白，并详细介绍了一些已被证明对皮肤分析有用的基本方案和检测方法。
