title: Characterization of RSF-1, the Caenorhabditis elegans homolog of the Ras-association domain family protein 1.
abstract: Mammals have 10 RASSF proteins, which are characterized by the Ras-association (RA) domain. Among them, RASSF1 to RASSF6 have the Salvador/RASSF/Hippo (SARAH) domain and form the subclass C-terminal RASSF proteins. Drosophila genome has a single C-terminal RASSF, dRASSF. All these RASSF proteins are related to the tumor suppressive Hippo pathway, and are considered to function as tumor suppressors. Caenorhabditis elegans T24F1.3 encodes a protein with the RA and the SARAH domains. The amino acid sequences are 40% and 55% similar to those of RASSF1 in the RA and the SARAH domains, respectively. We have characterized T24F1.3 gene product and named it RSF-1 as RASSF1 homolog. RSF-1 is widely expressed in epithelial cells. About 14% rsf-1 mutants exhibit defects in embryonal morphogenesis and the actin disorganization. The combinatorial synthetic lethal analysis demonstrates that the lethality is enhanced to more than 80% in rsf-1 mutants with the WASP-family verprolin homologous protein complex-related gene depletions and corroborates the implication of RSF-1 in the regulation of actin cytoskeleton. In rsf-1 mutants, the structures of muscle actin are preserved, but the swimming ability is impaired. Although we could not detect the direct physical interaction of LET-60 with RSF-1, rsf-1 mutants suppress the multivulva phenotype of the active let-60 mutants, suggesting that rsf-1 genetically interacts with the Ras signaling.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwasa
authors.forename: Hidehito
authors.initials: H
authors.lastname: Kuroyanagi
authors.forename: Sainawaer
authors.initials: S
authors.lastname: Maimaiti
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000235:genetics*; D004625:Embryo, Nonmammalian; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017385:Sequence Homology; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C517506:RASSF protein, Drosophila; C578982:RSF-1 protein, C elegans; C066646:let-60 protein, C elegans; D018631:ras Proteins