核糖体蛋白RPS8对蛋白质翻译的影响及其机制的研究.pdf

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1、学校代码:10246学号:082101019论文题目核糖体蛋合RPSS对蛋合质翻译的影响及其机制的研究院系:上海医学院专业:生物化学与分子生物学姓名:郝宇晴指导教师:顾建新教授导师组成员:阮元元讲师完成日期:2011年4月22日目录中文摘要················································································，……1英文摘要·····································，····································

2、·······……3第一部分:CDKllp46与RPSS相互作用并协同抑制蛋白质翻译的研究前言·······················································································……5材料与方法··············································································……7结果·························································

3、······························……18讨论·······················································································……27参考文献·················································································……29第二部分:即58的磷酸化修饰对蛋白质翻译调控的影响前言·······································

4、··，·············································……32材料与方法··············································································……34结果·······················································································……39讨论················································

5、·······································……43参考文献·················································································……44第三部分:综述:mTORCI介导蛋白质翻译调控的分子机制及其相关疾病的研究进展…46后记:硕士期间发表论文和所获奖励······················································……63致谢································

6、·······················································……64复旦大学2011届硕士毕业论文中文摘要第一部分cDKllp46与RPss相互作用并协同抑制蛋白质翻译的研究Cyelin一dependentkinase11(CDKll)蛋白家族，即pITSLRE蛋白激酶家族，是一类丝/苏氨酸蛋白激酶，其功能与细胞周期调控、肿瘤的发生以及细胞凋亡相关。研究发现，细胞在发生凋亡过程时，全长的cDKllPllo或者cDKllp58被caspase剪切，产生一个分子量大小约46一50kDa的蛋白，含有CDKll蛋白梭

7、基端的激酶活性区域。进一步研究发现CDKIlp46在细胞凋亡中发挥重要的作用，但具体机制尚不明确。我们通过Hispul卜down联合质谱分析发现核糖体小亚基蛋白58(”58)为eDKIlp46相互作用蛋白。GSTpull一down和免疫共沉淀实验验证了CDKllp46和RPSS在体外与体内均存在相互作用，免疫荧光共聚焦分析也揭示了它们在细细胞核内存在共定位。体外激酶实验发现，RPSS并不是CDKllp46的底物。进一步的功能研究表明，CDKllp46和卿58协同抑制帽依赖(eap一dependent)以及帽非依赖(IRES一d即endent)的蛋白质翻译，并

8、且协同提高了细胞对于Fas配体诱导凋亡的敏感性。我们