泛素化的功能及其意义

Role of Protein Ubiquitination and its Functional Importance

泛素化被定义为将泛素分子共价结合到靶蛋白上,是蛋白质组中最普遍的翻译后修饰之一.然而,泛素化不仅参与蛋白质数量的调节,不同的泛素化链长度(单泛素化、多泛素化以及多聚泛素化)及多种多样的泛素化链类型(连接通过Met1,Lys6,Lys11,Lys27,Lys29,Lys33,Lys48和Lys63),泛素化还在蛋白质活性、蛋白-蛋白相互作用以及蛋白质亚细胞定位中发挥极为重要的调控功能.由于泛素化的多样性与多价性,泛素化广泛参与各种生理过程,包括细胞增殖、凋亡、自噬、内吞、DNA损伤修复以及免疫应答.另外,泛素化失调在疾病中也发挥重要作用,如癌症、神经退行性病变、肌肉营养不良、免疫疾病以及代谢综合征.而尤其对于肿瘤以及神经退行性病变,针对泛素化通路的调控已被认为是肿瘤及神经退行性病变的一种有前景的治疗策略.

Ubiqutination, defined as the covalent attachment of ubiquitin to the target proteins, is one of the most important post-translational modifications（PTMs） of proteome. However, ubiquitination not only involves in the regulation of protein abundance, but also plays a role in the regulation of protein activity, interaction and subcellular localization. Ubiquitination is variable in length（monoubiquination, multiubiquitination and polyubiquination） and is different in ubiquitin chain types（linked via Met1, Lys6, Lys11, Lys27, Lys29, Lys33, Lys48 and Lys63）. Due to its diversity and multivalency, ubiquitination orchestrates numerous aspects of cell biology including cell proliferation, apoptosis, autophagy, endocytic trafficking, DNA damage repair and immunity response. Thus, dysregulation of ubiquitination has been associated with a wide spectrum of diseases including cancer, neurodegenerative disorders, muscle dystrophies, immune pathologies and metabolic syndromes. Therefore, targeting ubiquitination pathway has been demonstrated a promising therapeutic strategy in important diseases especially cancer and neurodegenerative disorders.