Muller S, Schwartz L M
Institut de Biologie Moléculaire et Cellulaire, UPR 9021 CNRS, Strasbourg, France.
Bioessays. 1995 Aug;17(8):677-84. doi: 10.1002/bies.950170804.
Ubiquitin is the most phylogenetically conserved protein known. This 8,500 Da polypeptide can be covalently attached to cellular proteins as a posttranslational modification. In most cases, the addition of multiple ubiquitin adducts to a protein targets it for rapid degradation by a multisubunit protease known as the 26S proteasome. While the ubiquitin/26S proteasome pathway is responsible for the degradation of the bulk of cellular proteins during homeostasis, it may also be responsible for the rapid loss of protein during the programmed death of certain cells, such as skeletal muscle during insect metamorphosis. In addition, alterations in the expression and regulation of ubiquitin may play significant roles in pathological disorders. For example, dramatic increases in ubiquitin and ubiquitin-protein conjugates are observed in a wide variety of neurodegenerative disorders, including Alzheimer's disease. Patients suffering from the autoimmune disease systemic lupus erythematosus generate antibodies reacting with ubiquitin and ubiquitinated histones. At present, it is not known whether these changes in ubiquitin expression and regulation initiate pathological changes in these diseases or if they are altered as a consequence of these disorders.
泛素是已知在系统发育上最保守的蛋白质。这种8500道尔顿的多肽可作为一种翻译后修饰与细胞蛋白质共价连接。在大多数情况下，向一种蛋白质添加多个泛素加合物会使其被一种称为26S蛋白酶体的多亚基蛋白酶快速降解。虽然泛素/26S蛋白酶体途径在稳态期间负责大部分细胞蛋白质的降解，但它也可能在某些细胞的程序性死亡过程中导致蛋白质的快速丢失，比如昆虫变态过程中的骨骼肌。此外，泛素表达和调控的改变可能在病理紊乱中起重要作用。例如，在包括阿尔茨海默病在内的多种神经退行性疾病中，观察到泛素和泛素 - 蛋白质缀合物显著增加。患有自身免疫性疾病系统性红斑狼疮的患者会产生与泛素和泛素化组蛋白反应的抗体。目前，尚不清楚泛素表达和调控的这些变化是引发了这些疾病中的病理变化，还是由于这些疾病而发生改变。
