Doherty Fergus J, Dawson Simon, Mayer R John
Laboratory of Intracellular Proteolysis, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
Essays Biochem. 2002;38:51-63. doi: 10.1042/bse0380051.
Intracellular proteins are targeted for degradation by the covalent attachment of chains of the small protein ubiquitin; a process known as ubiquitylation. Many proteins are phosphorylated prior to ubiquitylation, and therefore ubiquitylation and degradation of these proteins is regulated by kinase activity and signalling cascades. Many ubiquitylated proteins are degraded by the 26 S proteasome complex, which is found in the cytosol and nucleus. The 26 S proteasome consists of a 20 S core with proteolytic activity and 18 S regulatory complexes containing ATPases and ubiquitin-chain-binding proteins. Proteins degraded by the ubiquitin-proteasome pathway include cyclins and other regulators of the cell cycle, and transcription factors. Abnormal polypeptides are also degraded by the ubiquitin pathway, including abnormal polypeptides in the endoplasmic reticulum, which are translocated back out of the endoplasmic reticulum prior to ubiquitylation and degradation by the proteasome. The ubiquitin-proteasome pathway is implicated in numerous diseases including cancer and neurodegenerative diseases.
细胞内蛋白质通过与小蛋白泛素的链共价连接而被靶向降解，这一过程称为泛素化。许多蛋白质在泛素化之前会被磷酸化，因此这些蛋白质的泛素化和降解受激酶活性和信号级联反应调控。许多泛素化的蛋白质被26S蛋白酶体复合物降解，该复合物存在于细胞质和细胞核中。26S蛋白酶体由具有蛋白水解活性的20S核心和包含ATP酶及泛素链结合蛋白的18S调节复合物组成。通过泛素-蛋白酶体途径降解的蛋白质包括细胞周期蛋白和细胞周期的其他调节因子以及转录因子。异常多肽也通过泛素途径降解，包括内质网中的异常多肽，这些多肽在被蛋白酶体泛素化和降解之前会从内质网中转运出来。泛素-蛋白酶体途径与包括癌症和神经退行性疾病在内的多种疾病有关。
