蛋白质泛素化降解途径治疗多发性骨髓瘤的研究进展-内科学(血液)专业论文.docx

重庆医科 重庆医科大学硕士研究生学位论文 万方数据 万方数据 英汉缩略语名词对照 英文缩写 英文全称 中文全称 UPP ubiquitin-proteasome path—way 泛素-蛋白酶体通路 SUMO-1 Small ubiquitin-related modifier-l 泛素相关修饰蛋 1 USP ubiquitin-proteasome system 泛素特异性蛋白酶 Skp2 S-phasekinase associated protein2 S 期激酶相关蛋白 MM multiple myeloma 多发性骨髓瘤 Mdm2 Murine double minute 双微体 2 基因 Mcl1 myeloid cell leukemia—1 髓细胞白血病 1 基 因 UCHL5 Ubiquitin carboxyl-terminal hydrolase isozyme L5 泛素 C-末端水解酶 5 IL-6 interleukin-6 白细胞介素- 6 PI3K XIAP phosphoinositide-3-kinase X-linked inhibitor of apoptosis protein 磷酯酰肌醇 3 激酶 X 连锁凋亡抑制蛋 白 SAPK stress-activated protein kinase 应激活化蛋白激酶 MAPK mitogen-activated protein kinase 丝 裂 原 活 化 蛋 白 激 酶 1 蛋白质泛素化降解途径治疗多发性骨髓瘤的研究进展 摘 要 泛素是广泛存在于真核生物细胞中的一种高度保守的蛋白质。泛素 分子通过泛素活化酶、泛素结合酶、泛素连接酶与靶蛋白结合，经由 泛素-蛋白酶体通路吞噬、降解靶蛋白。该通路是细胞内蛋白质选择性 降解的重要途径之一。是真核细胞内重要的蛋白质质控系统，主要降 解细胞内 80%-90%泛素化的蛋白质。泛素化降解途径参与调节细胞周 期、增殖、凋亡、分化、转移、基因表达、转录调节、信号传递、损 伤修复、炎性免疫等几乎一切生命活动。当该途径超出正常生理作用 时，可以通过减弱生长抑制作用、减少细胞凋亡、促进血管生成引发 各种肿瘤。本文就蛋白质泛素化降解途径在多发性骨髓瘤的研究进展 做一综述。 关键词：泛素化,泛素-蛋白酶体通路，多发性骨髓瘤，硼替佐米， 卡非佐米 2 RESEARCH PROGRESS OF PROTEIN UBIQUITINATION DEGRADATION PATHWAY IN THE TREATMENT OF MULTIPLE MYELOMA ABSTRACT Ubiquitin is a highly conserved protein widely exists in eukaryotic cells. Ubiquitin molecules are bind to the target protein through the ubiquitin activating enzymes, ubiquitin conjugating enzymes, ubiquitin ligase and then engulf and degrade target protein through the ubiquitin proteasome pathway . ubiquitin proteasome pathway is one of the important ways of intracellular protein degradation.It’s an important system of protein quality controlling in the eukaryotic cells, degradation ubiquitinated proteins in 80%-90% cells.Ubiquitin degradation pathway involves in cell cycle regulation, proliferation, apoptosis,differentiation, metastasis, gene expression, transcription regulation, signal transduction,damage repair, inflammatory immune and almost all aspects of life activities. Once exceeds it’s normal physiological function, it will weaken the growth inhibition, reduce a