RAN cycle and cellular senescence

RAN 周期和细胞衰老

基本信息

批准号：
23657130
负责人：
YONEDA Yoshihiro
金额：
$ 2.58万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2011
资助国家：
日本
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23657130/
关键词：
核輸送細胞老化 Ran importin RanBP1

项目摘要

The small GTPase Ran, Ras-related nuclear protein, plays important roles in multiple fundamental cellular functions such as nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation, by binding to either GTP or GDP as a molecular switch. During the long-term culture of normal mammalian cells, I found that the endogenous Ran level gradually reduced in a passage-dependent manner. To examine the physiological significance of Ran reduction, I first performed small interfering RNA(siRNA)-mediated abrogation of Ran in human diploid fibroblasts. Ran-depleted cells showed several senescent phenotypes. Furthermore, I found that nuclear accumulation of importinα, which was also observed in cells treated with siRNA against CAS, a specific export factor for importinα, occurred in the Ran-depleted cells before the cells showed senescent phenotypes. Further, the CAS-depleted cells also exhibited cellular senescence. Indeed, importinα gradually accumulated in a passage-dependent manner. Thus, reduction in Ran levels causes nuclear accumulation of importinα, leading to cellular senescence in normal cells. The amount of intracellular Ran may be critically related to cell senescence. The cellular aging process may proceed through gradual regression of Ran-dependent nucleocytoplasmic transport competency.

小型GTPase运行，与RAS相关的核蛋白质端口，有丝分裂的纺锤体组件和核包膜形成，通过在正常Mamalian细胞的长期培养中与GTP或GDP作为分子开关结合。逐渐减少了thysiogal的含量。进口因子的特异性因素在细胞中出现在延伸的细胞中，表现出衰老的表型，CAS depledeppled的celso确实表现出细胞衰老。在正常的细胞中，ULAR可能与细胞鼻子中心密切相关。

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The role of Rael in Nup98-fusion mediated leukemogenesis

Rael 在 Nup98 融合介导的白血病发生中的作用

DOI：
10.4161/cc.10.12.15759
发表时间：
2011
期刊：
Cell Cycle.
影响因子：
0
作者：
Oka;M.;Yoneda;Y.
通讯作者：
Y.

Targeted disruption of one of the importin α family members leads to female functional incompetence in delivery

DOI：
10.1111/j.1742-4658.2011.08079.x
发表时间：
2011-05-01
期刊：
FEBS JOURNAL
影响因子：
5.4
作者：
Moriyama, Tetsuji;Nagai, Masahiro;Yoneda, Yoshihiro
通讯作者：
Yoneda, Yoshihiro

Mice lacking Ran binding protein 1 are viable and show male infertility

DOI：
10.1016/j.febslet.2011.02.002
发表时间：
2011-03
期刊：
FEBS Letters
影响因子：
3.5
作者：
Masahiro Nagai;Tetsuji Moriyama;R. Mehmood;K. Tokuhiro;M. Ikawa;M. Okabe;Hiromitsu Tanaka;Y. Yoneda
通讯作者：
Masahiro Nagai;Tetsuji Moriyama;R. Mehmood;K. Tokuhiro;M. Ikawa;M. Okabe;Hiromitsu Tanaka;Y. Yoneda

The small GTPase Ran and Ran-binding proteins

小 GTPase Ran 和 Ran 结合蛋白