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C. elegans Rassf homolog, rasf‐1 , is functionally associated with rab‐39 Rab GTP ase in oxidative stress response
Author(s) -
Takenaka Motohiko,
Inoue Hideki,
Takeshima Atsushi,
Kakura Tomonori,
Hori Toshiyuki
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12028
Subject(s) - rab , gtpase , caenorhabditis elegans , biology , mutant , microbiology and biotechnology , effector , gtp' , biochemistry , gene , enzyme
The Ras association domain family (Rassf) is one of the Ras effectors, which can bind to several GTP ‐charged Ras‐like GTP ases. The Rassf proteins are widely conserved beyond species from nematode to human. To explore the novel functions of Rassf proteins, we took advantage of nematode C. elegans as a model animal with only one Rassf homolog, T24F1.3 ( rasf‐1 ). The rasf‐1 ‐mutant as well as rasf‐1 ‐knockdown animals were found to be more sensitive to oxidative stress of arsenite than in wild type, indicating that rasf‐1 is 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 GTP ase 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‐39 mutant animals were also sensitive to oxidative stress, which was dependent on rasf‐1 according to the epistasis analysis. Moreover, Rassf1 and Rab39, mammalian homologs of rasf‐1 and rab‐39 , respectively, were shown to interact with each other in vitro . These results indicate that the RASF ‐1 functionally interacts with RAB ‐39 and that the interaction between their homologs is conserved in mammals.