THE ROLE OF P97 IN POST MITOTIC GOLGI RE-ASSEMBLY

P97 在有丝分裂后高尔基体重组中的作用

• 批准号: 6635787
• 负责人: Albert E Price
• 金额: $ 2.41万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6635787
• 关键词: Golgi apparatus; adenosinetriphosphatase; cell cycle; cofactor; enzyme substrate; laboratory rat; molecular assembly /self assembly; morphology; protein structure function

The Golgi complex in mammalian cells fragments during mitosis and these fragments are segregated between the two daughter cells. The post- mitotic re-assembly of the Golgi involves two related membrane ATPases, p97 and NSF. While p97 is highly abundant and evolutionarily more ancient than NSF, comparatively little is known of its function. I propose to determine the substrates of this ATPase in post-mitotic Golgi re-assembly by analyzing the formation of Golgi SNARE complexes with p97 and it's co-factor, p47. Using this method as a starting point, the role of p97 in Golgi re-assembly will be investigated. Clues as to the function of p97 suggest that it's action on Golgi SNARES and/or other substrates may be regulated by the mitotic state of the cell and that it may play a role distinct from that of NSF by acting on different types of SNARE complexes. Also to be investigated is the hypothesis that p97 and NSF act on morphologically distinct regions of the Golgi membrane. Answers to these questions will provide new insights into the effect of the cell cycle on membrane dynamics and the molecular mechanisms of organelle assembly.

哺乳动物细胞中的高尔基复合体在有丝分裂过程中产生碎片，这些碎片在两个子细胞之间分离。高尔基体的有丝分裂后重新组装涉及两种相关的膜 ATP 酶：p97 和 NSF。虽然 p97 的含量非常丰富，而且在进化上比 NSF 更古老，但人们对其功能知之甚少。我建议通过分析高尔基体 SNARE 复合物与 p97 及其辅助因子 p47 的形成来确定有丝分裂后高尔基体重新组装中该 ATP 酶的底物。以此方法为起点，将研究 p97 在高尔基体重组中的作用。关于 p97 功能的线索表明，它对高尔基体 SNARES 和/或其他底物的作用可能受到细胞有丝分裂状态的调节，并且它可能通过作用于不同类型的 SNARE 复合物而发挥与 NSF 不同的作用。还需要研究的是 p97 和 NSF 作用于高尔基膜形态上不同区域的假设。这些问题的答案将为细胞周期对膜动力学的影响和细胞器组装的分子机制提供新的见解。

项目成果

Strategic Incorporation of Fluorine into Taxoid Anticancer Agents for Medicinal Chemistry and Chemical Biology Studies.

• DOI: 10.1016/j.jfluchem.2016.12.016
• 发表时间: 2017-06
• 期刊: Journal of fluorine chemistry
• 影响因子: 1.9
• 作者: Ojima I