B23通过抑制Eg5 ATP酶活性抑制Eg5对微的解聚.docxVIP

优秀毕业论文 精品参考文献资料 Abstract ABSTRACT Nucleophosmin／B23，all abundant nucleolar protein，plays multiple roles in eeU growth and proliferation．There are two B23 isoforms．Subtype 1，which is the full length of B23，is 35 amino acids longer than Subtype 2．C—terminus of B23，which is called DNA and RNA Binding Domain(DRBD)，iS tend to mutanted．，and its mutations could induce Acute‘myeloid leukemia(AML)．It is reported that B23 mutations lead to aberrant localization of the B23 protein into the cytoplasm and promote AML occurrence．Despite its functions inside the nucleus is well—studied， functions of B23 in the cytoplasm remains elusive．Therefore，it is unclear exactly that how B23 mutations lead to AML．We then tried to find the meaning of B23 locates in the cytos01． Firstly,a Yeast··Two·-hybrid system Was used to screen B23 novel interact partners．And a member of the kinesin family,E95，was found and identified to interact with B23．It is further proved that B23 directly interacts with E95 in the cytos01．This evidences give some indications about the function of B23 in cytoplasm． An interesting result was then found that in opposite to E95，B23 promotes microtubule(MT)polymerization．This Was the first evidence that B23 plays an important role in regulating MT dynamics in cytoplasm． Further results showed that B23 regulates MT dynamics by directly inhibiting E95 ATPase activity．It makes senses for studying novel B23 functions．Furthermore， as E95 is an important anti—neoplasmic drug target，and wild type B23 could inhibit AML development，whether the inhibitors of E95 such as mimics of DRBD of B23 could be used in treating AML patients is of clinical interest． In a word，our works suggest that B23 has an important function in cytoplasm． Keywords：B23，E95，cancer clinical treatment，microtubule dynamic Il  中国科学技术大学学位论文原创性声明 本人声明所呈交的学位论文，是本人在导师指导下进行研究工作所取得的 成果。除已特别加以标注和致谢的地方外，论文中不包含任何他人已经发表或 撰写过的研究成果。与我一同工作的同志对本研究所做的贡献均已在论文中作 了明确的说明。 作者签名： 签字日期地棚 中国科学技术大学学位论文授权使用声明 本人授权中国科学技术大学拥??学位论文的部分使