MECHANISMS AND FUNCTION OF PROTEIN DEGRADATION

蛋白质降解的机制和功能

• 批准号: 6140032
• 负责人: TUDEVIIN GAN ERDENE
• 金额: $ 3.63万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6140032
• 关键词: Asia; SDS polyacrylamide gel electrophoresis; active sites; adenosine triphosphate; affinity chromatography; complementary DNA; electrospray ionization mass spectrometry; endopeptidases; enzyme activity; high performance liquid chromatography; ion exchange chromatography; isozymes; molecular cloning; oligonucleotides; protein degradation; protein sequence; recombinant proteins; ubiquitin

Ubiquitin is a highly conserved eukaryotic protein that has been suggested to play a key role in interacellular protein degradation, cell cycle regulation, DNA repair, recombination, chromatin structure, stress response, programmed cell death, and the mechanism of receptor action. In all cases it appears to exert its function by being covalently attached to target proteins by an amide bond between the C-terminal glycine of ubiquitin and an alpha or epsilon amino group on the labeled protein. A large number of members of the ubiquitin-specific processing protease (UBP) family have been identified. These proteases process the primary gene products, remove ubiquitin from other protein, and dissassemble the polyubiquitin degradation signal. In addition to ubiquitin, several other eukaryotic proteins contain ubiquitin-like domains. We will purify and characterize processing proteases that act upon the interferon-induced ubiquitin cross-reacting protein and examine their mechanism and specificity. This work will test the hypothesis that ubiquitin-like proproteins are processed by isoforms of the UBP family. Whether the hypothesis is proved or not, we will have identified the processing proteases that may be involved.

泛素是一种高度保守的真核蛋白，已被认为在细胞间蛋白降解、细胞周期调节、DNA 修复、重组、染色质结构、应激反应、程序性细胞死亡和受体作用机制中发挥关键作用。 在所有情况下，它似乎都是通过泛素 C 端甘氨酸与标记蛋白上的 α 或 ε 氨基之间的酰胺键共价连接至靶蛋白来发挥其功能。 泛素特异性加工蛋白酶 (UBP) 家族的大量成员已被鉴定。这些蛋白酶处理初级基因产物，从其他蛋白质中去除泛素，并分解多泛素降解信号。 除了泛素之外，其他几种真核蛋白也含有泛素样结构域。 我们将纯化和表征作用于干扰素诱导的泛素交叉反应蛋白的加工蛋白酶，并检查其机制和特异性。 这项工作将检验泛素样前蛋白由 UBP 家族亚型加工的假设。 无论该假设是否得到证实，我们都将确定可能涉及的加工蛋白酶。