Nephrology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
J Am Soc Nephrol. 2011 May;22(5):821-4. doi: 10.1681/ASN.2010090958. Epub 2011 Apr 7.
Proteins in all cells turnover continuously such that rigorous control of proteolysis is required to govern levels of proteins with vastly different half-lives and actions including those regulating transcription, metabolic pathways, or the breakdown of muscle proteins to amino acids used in gluconeogenesis or the synthesis of new proteins. Critical cellular functions would be disrupted without precise regulation of protein degradation. Thus, it is surprising that the bulk of protein in all cells is degraded by the ATP-dependent, ubiquitin-proteasome system. The system achieves remarkable specificity by selective conjugation of ubiquitin (Ub) to a doomed protein in a process catalyzed by >1000 ubiquitin ligases that recognize individual substrate proteins. Because the pathogenesis of certain kidney diseases and their complications are linked to the function of the ubiquitin-proteasome system, understanding its mechanisms could lead to novel therapies.
所有细胞中的蛋白质都在不断更新，因此需要严格控制蛋白质水解，以调节半衰期和作用差异极大的蛋白质水平，这些蛋白质包括调节转录、代谢途径，或肌肉蛋白分解为用于糖异生或新蛋白质合成的氨基酸。如果不能精确调控蛋白质降解，细胞的关键功能就会受到破坏。因此，令人惊讶的是，所有细胞中的大部分蛋白质都是由依赖于 ATP 的泛素-蛋白酶体系统降解的。该系统通过 >1000 种泛素连接酶的催化作用，选择性地将泛素（Ub）连接到注定要被降解的蛋白质上，从而实现显著的特异性，这些泛素连接酶能够识别单个底物蛋白。由于某些肾脏疾病及其并发症的发病机制与泛素-蛋白酶体系统的功能有关，因此了解其机制可能会带来新的治疗方法。
