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A study on the control mechanisms of starvation response and cell differentiation, using the developmental system of Dictyostelium

利用盘基网柄菌发育系统研究饥饿反应和细胞分化的控制机制

基本信息

批准号：
16370030
负责人：
MAEDA Yasuo
金额：
$ 8.58万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16370030/
关键词：
growth differentiation starvation pattern formation mitochondria Dictyostelium 飢餓応答 TRAP-1 cdc-25 PSV

项目摘要

This work has been done to elucidate precisely genes and their functions, which are involved in control of cellular growth and differentiation, using the developmental system of Dictyostelium cells. New findings done by this work are as follows. (1) The dial gene that are specifically expressed coupling with differentiation of cells from the growth/differentiation transition point (GDT-point) in the cell cycle was found to shares the promoter region with other gene (impA) ; the impA is specifically expressed during the growth phase, while the dial at the initiation of differentiation. By promoter analyses, the regions that regulate their transcription were precisely specified. (2) Dd-TRAP1, a Dictyostelium homologue of mitochondria-localized HSP90 (TRAP-1) was found to be closely involved in the prestarvation response (PSR) and subsequent differentiation after starvation of cells ; the suppression of Dd-trap 1 expression by the RNAi method greatly inhibits the PSR and therefore the initiation of differentiation f starving cells. (3) Dd-TRAP1 changes its localization depending on the cell densities during the growth phase ; Dd-TRAP1 moves extensively to the cell cortex from mitochondria at low cell densities, while it returns again to mitochondria from the cell cortex at higher cell densities. (4) The return of, Dd-TRAP1 is induced by a novel prestarvation-factor-3 (PSF-3) and required for subsequent differentiation of starving cells. (5) A Dictyostelium homologue (DNG1) of the tumor suppressor (ING1) was found to be closely involved in cell differentiation as well as in growth through histone modification. Incidentally, exhaustive analyses of genes involved in starvation response and initiation of differentiation are now in advance as collaborative works with Drs. Adam Kuspa and Gad Shaulsky of Baylor Medical College.

本研究旨在利用盘基骨门细胞的发育系统，精确地阐明与细胞生长和分化有关的基因及其功能。本研究的新发现如下。(1)从细胞周期的生长/分化过渡点（GDT-point）特异性表达与细胞分化偶联的dial基因与其他基因（impA）共享启动子区域；impA在生长阶段特异性表达，而dial在分化开始阶段特异性表达。通过启动子分析，精确地指定了调控它们转录的区域。(2)发现线粒体定位HSP90 （TRAP-1）的盘基骨门同源物Dd-TRAP1密切参与细胞饥饿后的饥饿前反应（PSR）和随后的分化；通过RNAi方法抑制Dd-trap 1的表达，极大地抑制了PSR，从而抑制了饥饿细胞分化的开始。(3)生长期间，Dd-TRAP1的定位随细胞密度的变化而变化；当细胞密度较低时，Dd-TRAP1从线粒体广泛移动到细胞皮层，而当细胞密度较高时，它又从细胞皮层返回到线粒体。(4) Dd-TRAP1的返回是由一种新的饥饿前因子-3 （PSF-3）诱导的，并且是饥饿细胞后续分化所必需的。(5)发现抑癌因子ING1的盘基骨菌同源物（DNG1）通过组蛋白修饰密切参与细胞分化和生长。顺便说一句，与饥饿反应和分化启动有关的基因的详尽分析，现在已经作为与dr .。贝勒医学院的亚当·库斯帕和盖德·绍斯基。