EXPRESSION, STRUCTURE AND FUNCTION OF FILAGGRIN

聚丝蛋白是一种主要的终末分化产物， 分化哺乳动物表皮细胞，这被认为是 参与角蛋白的聚集和特定排列 在分化的最后阶段的中间丝。因此 聚丝蛋白是一个重要的例子， 蛋白我们已经分离了cDNA和基因组克隆，它们表明， 丝聚蛋白最初表达为大的多蛋白前体， 聚丝蛋白原，其随后被蛋白水解加工成 单个功能性聚丝蛋白分子。基因的结构 人类原丝聚集蛋白现已确定：它由3个外显子组成 由2个内含子分开，第一个内含子很大（约10 kbp）。的 人和小鼠聚丝蛋白原的氨基末端具有两个 EF-手型的功能性钙结合结构域。有 内含子和外显子的多重选择性剪接的证据， 产生一系列其他钙结合蛋白， 功能我们已经构建了基因组克隆， 转基因小鼠我们已经开始对监管进行系统分析 控制聚丝蛋白原基因系统表达的序列。 我们已经确定达特丝蛋白聚集角蛋白和波形蛋白 通过离子相互作用形成中间丝。

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.