EPIDERMAL TRANSGLUTAMINASES

表皮谷氨酰胺转胺酶

• 批准号: 5200634
• 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/5200634
• 关键词: active sites; antibody formation; cell differentiation; crosslink; dipeptides; enzyme activity; enzyme mechanism; gene deletion mutation; genetic promoter element; human tissue; isozymes; keratinocyte; lysine; membrane proteins; protein glutamine gamma glutamyltransferase; protein structure function; skin

Transglutaminases form an isodipeptide crosslink between an acceptor amide group of a protein bound glutamine residue and a donor e-NH2 of a protein bound lysine residue, thereby forming a highly insoluble macromolecular complex. In the epidermis, three enzymes are thought to be involved in crosslinking of certain defined structural proteins to form an insoluble cornified cell envelope, and are transglutaminases 1, 2 and 3. We are studying in detail the roles of the human transglutaminase 1 and 3 enzymes. By use of new specific antibodies, we have found that the transglutaminase 1 system in keratinocytes or foreskin epidermis is very complex, since it exists in multiple soluble as well as membrane-bound forms. The most active of these, a 67 and 33kDa complex held together by secondary forces, is generated during terminal differentiation in these cells by proteolytic cleavage of specific sites that are conserved in the family of transglutaminases. This is similar to the known proteolytic activation of the transglutaminase 3 system. The proximal promoter region of the transglutaminase 3 gene is located within the first 125 bp above the transcription initiation start site, and consists of an Sp1 motif modulated by two adjacent ets-like motifs. These are sufficient to connote epithelial specific expression to this gene.

转谷氨酰胺酶在受体之间形成异二肽交联物 蛋白质结合的谷氨酰胺残基和A的供体e-NH_2的酰胺基 蛋白质结合赖氨酸残基，从而形成高度不溶的 大分子复合体。在表皮中，有三种酶被认为是 参与某些特定结构蛋白的交联化 形成不溶的角化细胞膜，是转谷氨酰胺酶1， 2和3.我们正在详细研究人类的角色 转谷氨酰胺酶1和3酶。通过使用新的特异性抗体，我们 发现角质形成细胞中的转谷氨酰胺酶1系统或 包皮表皮非常复杂，因为它以多种可溶性形式存在。 以及膜结合形式。其中最活跃的是67岁和 33 kDa的杂岩由次级力量聚集在一起，是在 这些细胞的终末分化是通过蛋白水解酶的裂解 转谷氨酰胺酶家族中保守的特定位点。 这类似于已知的蛋白水解性激活 转谷氨酰胺酶3系统。基因的近端启动子区域 谷氨酰胺转氨酶3基因位于谷氨酰胺转氨酶基因的前125个碱基内。 转录起始位置，由Sp1基序组成 由两个相邻的ETS类基序调制。这些都足以 提示该基因在上皮细胞中的特异性表达。