EXPRESSION, STRUCTURE AND FUNCTION OF FILAGGRIN

丝聚蛋白的表达、结构和功能

• 批准号: 3792228
• 负责人: P STEINERT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792228
• 关键词: RNA splicing; cell differentiation; cytoskeletal proteins; gene expression; genetic disorder; genetic regulatory element; genetically modified animals; human tissue; intermediate filaments; keratin; laboratory mouse; molecular cloning; nuclear magnetic resonance spectroscopy; pathologic keratinization; protein sequence; protein structure function; proteolysis; skin; structural genes; vimentin

Filaggrin is a major differentiation product of terminally differentiating mammalian epidermal cells, that is thought to be involved in the aggregation and specific alignment of keratin intermediate filaments during the final stages of differentiation. Thus filaggrin is an important example of an intermediate filament-associated protein. We have isolated both cDNA and genomic clones which show that filaggrin is initially expressed as a large polyprotein precursor, profilaggrin, which is subsequently proteolytically processed into individual functional filaggrin molecules. The structure of the gene for human profilaggrin has now been settled: it consists of 3 exons separated by 2 introns, the first of which is huge (about 10 kbp). The amino-terminal end of human and mouse profilaggrins possess two functional calcium binding domains of the EF-hand type. There is evidence for multiple alternate splicing of introns and exons, giving rise to a series of other calcium binding proteins of as yet unknown function. We have constructed genomic clones for the production of transgenic mice. We have begun a systemic analysis of regulatory sequences that control the expression of the profilaggrin gene system. We have determined tat filaggrin aggregates keratin and vimentin intermediate filaments by ionic interactions.

微丝蛋白是一种主要的终末分化产物 哺乳动物表皮细胞的分化，这被认为是 参与角蛋白的聚集和特异性排列 分化末期的中间丝。因此， 细丝结合蛋白是中间纤维相关的一个重要例子。 蛋白。我们已经分离了cdna和基因组克隆，这表明 丝状蛋白最初是作为一种大的多蛋白前体表达的， Profilaggrin，它随后被蛋白质分解处理成 单个功能丝状微丝蛋白分子。该基因的结构 人类侧写基因现已确定：它由3个外显子组成 由两个内含子分开，第一个内含子很大(约10kbp)。这个 人和小鼠Profilagrins的氨基末端具有两个 EF-HAND类型的功能性钙结合结构域。的确有 内含子和外显子多重交替剪接的证据，给出 上升为一系列其他未知的钙结合蛋白 功能。我们已经构建了基因组克隆，用于生产 转基因小鼠。我们已经开始对监管机构进行系统分析 控制profilaggrin基因系统表达的序列。 我们已经测定了TAT微丝蛋白聚合体角蛋白和波形蛋白 通过离子相互作用产生的中间纤维。