EXPRESSION, STRUCTURE AND FUNCTION OF FILAGGRIN

丝聚蛋白的表达、结构和功能

• 批准号: 2568363
• 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/2568363
• 关键词: apoptosis; cell differentiation; cytoskeletal proteins; gene expression; genetic promoter element; human tissue; intermediate filaments; keratin; keratinocyte; nuclear factor kappa beta; protein sequence; protein structure function; skin; transcription factor; transfection /expression vector

Filaggrin, the processed form of profilaggrin, is a major product of terminally differentiating mammalian epidermis. Based on in vitro experiments, fillaggrin is thought to be involved in the aggregation and specific alignment of keratin intermediate filaments during the final stages of development in the epidermis in vivo. This hypothesis has been explored by stable transfection into keratinocytes of a vector containing one fillaggrin repeat under the control of an inducible promoter. Upon activation of the promoter, the expressed filaggrin disrupts the keratin cytoskeleton due to aggregation of the filament near the nucleus, causes major shape changes in the cells. The cells die within 6 hours by apoptosis. We have explored the regulation of expression of the profilaggrin gene and have characterized the proximal promoter. An AP1 site and its cognate binding c-fos and c-jun proteins confer keratinocyte-specific expression to the gene, in concert with neighboring Sp1, ets-like, and NF-KB elements. We have discovered a novel ets transcription protein that seems to function in the regulation of expression of several genes in the epidermis, including profilaggrin.

聚丝蛋白是聚丝蛋白的加工形式，是聚丝蛋白的主要产物