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Jingdong book

泛素介导的蛋白质降解

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Jingdong book

泛素介导的蛋白质降解

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蛋白质是生物体内细胞和组织的基本构成物质，它还构成机体中参与调节各种细胞和生理活动的生命活性物质，包括催化体内各种生物化学反应的酶，调节机体生长、发育并行使正常生理功能的激素，抵御外来细菌病毒的抗体及免疫类物质，运载许多重要代谢物质、营养素的载体。当机体需要时，蛋白质还可以被代谢分解，释放出能量。几乎所有的蛋白质都处于不断的合成与分解的动态之中，细胞内蛋白质半衰期的差别很大，从几分钟到几年。
泛素介导的蛋白质降解通路控制着真核细胞内绝大多数蛋白质的选择性降解，是基因和蛋白质功能的主要调节者和终结者，并掌控着几乎所有动植物的生命活动。它的异常会导致癌症或神经退行性疾病等多种人类重大疾病的发生。因此，对该通路的调控已成为疾病治疗中的一种创新性方法。2003年，一种蛋白质降解的特异性抑制剂Velcade／PS-341已成功地应用于治疗多发性骨髓瘤。
虽然国外已有多本外文专著介绍泛素介导的蛋白质降解，但国内尚无同类中文书籍出版，很难满足我国读者的需要。本书系统而深入地介绍该领域的基本理论、实验技术及应用前景，共分八章：①蛋白质降解概论；②泛素、类泛素、泛素化及类泛素化；③泛素激活酶；④泛素载体蛋白；⑤泛素连接酶；⑥去泛素化及去泛素化酶；⑦蛋白酶体；⑧泛素一蛋白酶体通路与药物开发。除第一章外，每章包括基本理论和实验技术两个部分。本书可作为从事生命科学研究的研究生、科研人员，以及从事药物或相关产品研发的企业人员的参考书，也可作为有志从事生命科学研究的本、专科学生（包括理、工、农、林、医、环境等相关学科）的课外读物。
Author Description

邱小波，北京师范大学生命科学学院教授。1996年获得美国南加州大学分子药理与毒理专业的博士学位，1997-2005年在美国哈佛大学医学院T作，2005年回国工作。
王琛，中国科学院生物化学与细胞生物学研究所研究员。1998年于中国科学院上海生物化学研究所获博士学位，1998-2002年在美国University of Connecticut Health Center和University of Texas SouthwesternMedical Center工作。
王琳芳，中国工程院院士，中国医学科学院北京协和医学院一清华大学医学部基础医学研究所医学分子生物学国家重点实验室教授。1959年于北京协和医学院研究生毕业，1981-1983年在美国洛克菲勒大学人口委员会生物医学研究中心从事博士后研究。
Catalogue

第一章 蛋白质降解概论
第一节 泛素一蛋白酶体通路概述
第二节 泛素一蛋白酶体通路的异常与人类重大疾病的发生
第三节 溶酶体及其在蛋白质降解中的作用
第四节 泛素介导的蛋白质降解研究的历史背景、现状与前景
第二章 泛素、类泛素、泛素化及类泛素化
第一节 泛素及类泛素蛋白
第二节 泛素结合蛋白
第三节 泛素化及类泛素化
第三章 泛素激活酶E1
第一节 概述
第二节 泛素激活酶E1的表达和纯化
第三节 人泛素激活酶E1 APPBPl一UBA3异二聚体复合物的表达和纯化
第四节 激活酶E1 UbE1L的表达和纯化
第四章 泛素载体蛋白E2
第一节 概述
第二节 泛素载体蛋白IJbc4／5家族的表达和纯化
第三节 泛素载体蛋白Cdc34．和Ubct3·Mms2的表达和纯化
第四节 泛素载体蛋白Ubc12介导的NEDD8修饰反应
第五节 泛素载体蛋白ubc9的表达、纯化和活性鉴定
第六节 荧光共振能量转移方法分析suMO的修饰
第七节 检测E2-泛素硫酯中间产物形成的高通量方法
第五章 泛素连接酶
第一节 概述
第二节 实验技术
第六章 去泛素化及去泛素化酶
第一节 概述
第二节 实验技术
第七章 蛋白酶体
第一节 概述
第二节 蛋白酶体活性测定
第三节 蛋白酶体及其激活物的纯化与分析
第八章 泛素一蛋白酶体通路与药物开发
第一节 概述
第二节 蛋白酶体抑制剂
第三节 泛素连接酶抑制剂
第四节 用嵌合蛋白法启动底物蛋白质降解
主要专业名词英汉对照
Book Abstract

第一章 蛋白质降解概论
蛋白质降解调控着动植物体内几乎所有的生命活动。蛋白质在行使其功能后，需在特定的时空条件下被降解；蛋白质在合成、折叠、转运、或行使功能过程中发生错误或损伤时，需被及时降解和清除；食物中的蛋白质，也要经过蛋白质降解酶的作用降解为多肽或氨基酸才能被人体吸收。人类细胞中存在着两类主要的蛋白质降解途径，即溶酶体和泛素一蛋白酶体通路。前者无需能量，主要降解细胞外和细胞膜蛋白质；后者则是一种耗能的高效、特异的蛋白质降解过程，控制着动植物细胞内绝大多数蛋白质的降解。一百多年来，蛋白质生物合成的研究备受青睐，但蛋白质降解这一领域则被长期忽略。直到近几年，尤其是2004年关于泛素介导的蛋白质降解的发现获得诺贝尔奖以后，蛋白质降解研究才在国际上被引起广泛重视。人们现已清楚地认识到，蛋白质的降解与合成同样重要。本章将简要介绍泛素一蛋白酶体通路和溶酶体的组成、生理功能及其与疾病的关系，回顾泛素一蛋白酶体通路的研究历史，分析该领域的研究现状，并展望其研究前景。
第一节 泛素一蛋白酶体通路概述
蛋白质是生命活动的直接执行者，生命过程中几乎所有的环节都与蛋白质有关。“蛋白质”一词最早源于1838年，是从希腊文“proteios”衍生而来，意为首要的物质。一百多年来，科学家们已对蛋白质合成进行了大量的研究并取得了辉煌的成就，与其相关的研究至少已有五项被授予诺贝尔奖。蛋白质合成固然重要，但蛋白质降解对生命的意义并不亚于蛋白质合成。在人类基因组中，与蛋白质合成相关的基因约占1％，而与蛋白质降解相关的基因则超过3％。
Introduction

一百多年来，蛋白质合成的研究受到了广泛重视并取得丰硕的成果，已获得至少五次诺贝尔奖。然而，在很长时间内蛋白质降解的研究并未引起足够重视；直到2004年Ciechanover、Hershko和Rose因发现泛素介导的蛋白质降解而获得诺贝尔奖之后，这一情形才有明显改观。泛素介导的蛋白质降解通路是基因和蛋白质功能的主要调节者和终结者，控制着真核细胞内绝大多数蛋白质的降解。
该通路调控着儿乎所有动植物的生命活动，包括细胞增殖、分化、凋亡、DNA修复、转录和蛋白质质量控制等，并参与病原体的入侵、致病和人体的免疫应答等过程。它的异常会导致癌症和神经退行性疾病等人类多种重大疾病。一种该通路的特异性抑制剂Velcade/PS-341已于2003年成功地用于治疗多发性骨髓瘤。近十年来，与泛素化修饰方式类似的一系列蛋白质类泛素化修饰（包括SUMO、ISGI5、NEDD等）被发现，它们的生物学意义涉及细胞生命活动的各个方面。总之，该领域已成为现代生命科学研究的热点之一。我国在此领域虽然起步较晚，但正呈现蓬勃发展之势。
作为泛素介导的蛋白质降解领域的第一本中文专著，该书较为系统和深入地介绍了泛素介导的蛋白质降解的基本理论及相关实验技术。在全面介绍本领域研究进展的同时，也在一定程度上反映了我同科学家所取得的相关研究成果。该书的编者几乎都是国内活跃在第一线并在该领域奋斗多年的科学工作者。相信它的出版将会促进我国在这一关键领域的研究，并将惠及整个生命科学的发展。
陈竺
上海交通大学瑞金医院
中国人民共和国卫生部

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