C. elegans Rassf homolog, rasf-1, is functionally associated with rab-39 Rab GTPase in oxidative stress response.
C. elegans Rassf homolog, rasf-1, is functionally associated with rab-39 Rab GTPase in oxidative stress response.
复制标题
线虫 Rassf 同源物 rasf-1 在氧化应激反应中与 rab-39 Rab GTPase 功能相关。
DOI：
10.1111/gtc.12028
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发表时间：
2013
期刊：
影响因子：
2.1
通讯作者：
and Toshiyuki Hori
中科院分区：
文献类型：
--
作者：
Motohiko Takenaka;Hideki Inoue;Atsushi Takeshima;Tomonori Kakura;and Toshiyuki Hori
Ras相关结构域家族（Ras association domain family，Rassf）是Ras效应子之一，可与多个携带GTP的Ras样GTP酶结合。Rassf蛋白在从线虫到人类的物种之外是广泛保守的。为了探索Rassf蛋白的新功能，我们利用线虫C. elegansas是一种只有一个Rassf同源物T24F1.3（rasf-1）的模型动物。发现rasf-1-突变体以及rasf-1-敲低动物对亚砷酸盐的氧化应激比野生型更敏感，表明rasf-1参与氧化应激反应。接下来，我们通过酵母双杂交系统筛选与RASF-1相互作用的蛋白质，并将RAB-39 Rab GTdR鉴定为RASF-1的相互作用伴侣。我们不仅证实了这些分子之间的特异性结合，而且还证明了RASF-1结合GTP结合形式而不是GDP结合形式的RAB-39。重要的是，rab-39突变动物也对氧化应激敏感，根据上位性分析，氧化应激依赖于rasf-1。此外，Rassf-1和Rab 39分别是rasf-1和drab-39的哺乳动物同源物，在体外显示出相互作用。这些结果表明RASF-1与RAB-39在功能上相互作用，并且它们的同源物之间的相互作用在哺乳动物中是保守的。
The Ras association domain family (Rassf) is one of the Ras effectors, which can bind to several GTP‐charged Ras‐like GTPases. The Rassf proteins are widely conserved beyond species from nematode to human. To explore the novel functions of Rassf proteins, we took advantage of nematodeC. elegansas a model animal with only one Rassf homolog, T24F1.3 (rasf‐1). Therasf‐1‐mutant as well asrasf‐1‐knockdown animals were found to be more sensitive to oxidative stress of arsenite than in wild type, indicating thatrasf‐1is involved in oxidative stress response. We next screened for proteins that interact with RASF‐1 by the yeast two‐hybrid system and identified RAB‐39 Rab GTPase as an interacting partner of RASF‐1. We not only confirmed specific binding between these molecules but also demonstrated that RASF‐1 binds to GTP‐bound form but not GDP‐bound form of RAB‐39. Importantly,rab‐39mutant animals were also sensitive to oxidative stress, which was dependent onrasf‐1according to the epistasis analysis. Moreover, Rassf1 and Rab39, mammalian homologs ofrasf‐1andrab‐39, respectively, were shown to interact with each otherin vitro. These results indicate that the RASF‐1 functionally interacts with RAB‐39 and that the interaction between their homologs is conserved in mammals.