Ubiquitin in homeostasis, development and disease.
Ubiquitin in homeostasis, development and disease.
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泛素在稳态、发育和疾病中的作用。
DOI：
10.1002/bies.950170804
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Schwartz,LM
中科院分区：
文献类型：
--
作者：
Muller,S;Schwartz,LM
泛素是已知的在系统发育上最保守的蛋白质。这种8500Da的多肽可以作为翻译后修饰共价连接到细胞蛋白质上。在大多数情况下，将多个泛素加合物添加到蛋白质中，目标是通过一种名为26S蛋白酶体的多亚单位蛋白酶快速降解它。虽然泛素/26S蛋白酶体途径负责在动态平衡过程中大量细胞蛋白的降解，但它也可能与某些细胞在程序性死亡过程中蛋白质的迅速丢失有关，例如昆虫变态期间的骨骼肌。此外，泛素表达和调控的改变可能在病理障碍中发挥重要作用。例如，在包括阿尔茨海默病在内的各种神经退行性疾病中观察到泛素和泛素-蛋白质结合物的急剧增加。患有自身免疫性疾病系统性红斑狼疮的患者会产生抗体，与泛素和泛素化的组蛋白发生反应。目前，尚不清楚泛素表达和调控的这些变化是否启动了这些疾病的病理变化，或者它们是否因这些紊乱而改变。
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.