泛素-蛋白酶体途径在恶性肿瘤中的研究进展

Advances of Ubiquitin-Proteasome Pathway in Malignant Tumors

泛素-蛋白酶体途径(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。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、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密切相关。抑制泛素-蛋白酶体系统的过度表达可作为恶性肿瘤一种新的治疗手段。

The ubiquitin-proteasome pathway（UPP） is an important pathway for the intracellular proteins target degradation.Polymers of ubiquitin can be covalently attached to protein targets by a three-step（ubiquitin-activating enzyme,ubiquitin-conjugating enzymes,ubiquitin-protein ligases） conjugated cascade responses.The resulting ubiquitylated proteins are then recognized and degraded by the 26S proteasome.UPP is essential for many cellular processes,including apoptosis,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.It can be a new treatment for malignant tumors to inhibit the overexpression of the ubiquitin-proteasome system.