权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Clarification of mechanism of anamorsin, anti-apoptotic molecule

阐明抗凋亡分子阿莫辛的作用机制

基本信息

批准号：
17590996
负责人：
SHIBAYAMA Hirohiko
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590996/
关键词：
Anamorsin Yeast-two-hybrid PICOT PKCθ apoptosis 抗アポトーシス Yeast-two-hybrid法

项目摘要

We identified an anti-apoptotic molecule named anamorsin, which does not show any homology to known apoptosis regulatory molecules or cell growth related molecules. Anamorsin was found to act as an anti-apoptotic molecule in vivo since anamorsin -/- mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Anamorsin is predicted to work as a methyltransferase from its amino acid sequence, however, the precise mechanisms how anamorsin works have not been clarified. In order to reveal the mechanism, we tried to find the anamorsin binding molecules by yeast-two-hybrid assay. Picot (thioredoxin-like 2) was preferentially identified. We have shown that anamorsn and picot bind each other in vivo and in vitro. Furthermore, it was found that anamorsin binds with picot at 11-180 amino acids (N-terminal) position, while picot binds with anamorsin at 18-117 amino acids (N-terminal) position. Picot was originally identified as protein kinase C θ (PKCθ) binding protein, and thought to inhibit PKCθ activity of cell growth and survival. It is possible that anamorsin binds with picot and might modify picot activity of PKCθ inhibition. In the future, we will focus on reciprocal actions of anamorsin and picot in the cell growth and survival.

我们鉴定了一种名为anamorsin的抗凋亡分子，其与已知的凋亡调节分子或细胞生长相关分子没有任何同源性。发现Anamorsin在体内充当抗凋亡分子，因为anamorsin -/-小鼠在妊娠晚期由于胎肝（FL）中有缺陷的确定性造血而死亡。据预测，Anamorsin从其氨基酸序列作为甲基转移酶起作用，然而，Anamorsin如何起作用的精确机制尚未阐明。为了揭示其作用机制，我们尝试利用酵母双杂交技术寻找与无性素结合的分子。Picot（硫氧还蛋白样2）被优先鉴定。我们已经证明，anamorsn和picot在体内和体外相互结合。此外，发现anamorsin在11-180个氨基酸（N-末端）位置与picot结合，而picot在18-117个氨基酸（N-末端）位置与anamorsin结合。Picot最初被鉴定为蛋白激酶C θ（PKCθ）结合蛋白，并被认为抑制PKCθ活性影响细胞的生长和存活。可能是anamorsin与picot结合，并可能改变picot对PKCθ抑制的活性。今后，我们将重点研究无性型和皮考在细胞生长和存活中的相互作用。