Characterization of RSF-1, the Caenorhabditis elegans homolog of the Ras-association domain family protein 1

Exp Cell Res. 2013 Feb 1;319(3):1-11. doi: 10.1016/j.yexcr.2012.10.008. Epub 2012 Oct 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / isolation & purification
  • Caenorhabditis elegans Proteins / metabolism
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Drosophila Proteins / genetics*
  • Embryo, Nonmammalian
  • HEK293 Cells
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Homology
  • Tumor Cells, Cultured
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Drosophila Proteins
  • RASSF protein, Drosophila
  • RSF-1 protein, C elegans
  • let-60 protein, C elegans
  • ras Proteins