摘要
细胞内蛋白质的产生和降解必须保持着动态平衡,才能维持细胞的稳态和正常功能。泛素-蛋白酶体途径(ubiquitin-proteasome pathway,UPP)是细胞内蛋白质选择性降解的重要途径,泛素分子主要通过泛素活化酶、泛素结合酶和泛素-蛋白连接酶与靶蛋白结合形成一条多泛素链,将底物蛋白泛素化,使靶蛋白被26S蛋白酶体所识别和降解。UPP可高效并高选择性地降解细胞内蛋白质,尤其是一些短寿命的细胞周期调节蛋白、癌基因和抑癌基因产物以及变性变构蛋白等。泛素化过程是真核细胞内重要的蛋白质质控系统,参与细胞的多种生理活动过程,比如细胞凋亡、MHCⅠ类抗原的递呈、细胞周期以及细胞内信号传导等,对维持细胞正常的生理功能具有十分重要的意义。当泛素-蛋白酶体系统对靶蛋白的降解功能失常时,可以引起癌蛋白聚集、抑癌蛋白异常降解、突变细胞凋亡受阻和增殖加速,从而导致肿瘤的发生。UPP的异常改变不仅与恶性肿瘤的病因学有着直接关素,并且与恶性肿瘤的发展和预后有着密切的关系。
The generation and degradation of intracellular proteins must keep dynamic balance, which playsa key role to maintain cellular stable and normal functions. The ubiquitin proteasome pathway （UPP） is an important pathway for the intracellular proteins target degradation. Polymers of ubiquitin can be co valently attached to protein targets by a three-step （ubiquitin-activating enzyme, ubiquitinconjugating enzymes, ubiquitin-protein ligases） conjugated cascade responses. The resulting ubiquitylated proteins are then recognized and degraded by the 26S proteasome. UPP can degrade intraeellular proteins with high effect and selectivity, especially for cell cycle regulated proteins, oncoproteins, tumor suppressor proteins, and denaturalized proteins. UPP is essential for many cellular processes, including apoptosis, MHC class I antigen presentation, the cell cycle and intracellular signaling, which has a closed relationship with the cellular physiology and pathology. The malfunction of ubiquitin-proteasome system to the targeted proteins could enhance the effect of oncoproteins, reduce the amount of suppressor proteins, inhibit the apoptosis of mutated cells, and promote the proliferation, which are the reasons of carcinogenesis. Aberrations in the ubiquitination system are directly implicated in pathogenesis of certain malignancies, also have closed relations with their progression and prognosis.
出处
《中华肿瘤防治杂志》
CAS
2007年第19期1512-1515,共4页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30500582)
关键词
泛素-蛋白酶体途径
肿瘤
信号传导
药物靶标
综述文献
ubiquitin proteasome pathway
cancer
signal transduction
drug target
review literature
