Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68

The gld-1 gene of Caenorhabditis elegans is a germ-line-specific tumor suppressor gene that is essential for oogenesis. We have cloned the gld-1 gene and find that it encodes two proteins that differ by 3 amino acids. The predicted proteins contain a ∼ 170-amino-acid region that we term the GSG domain (GRP33/Sam68/GLD-1), on the basis of significant similarity between GLD-1, GRP33 from shrimp, and the Src-associated protein Sam68 from mouse (also described as GAPap62 from humans). A conserved structural motif called the KH domain is found within the larger GSG domain, suggesting a biochemical function for GLD-1 protein in binding RNA. The importance of the GSG domain to the function of gld-1 in vivo is revealed by mutations that affect 5 different conserved GSG domain residues. These include missense mutations in an absolutely conserved residue of the KH domain that eliminate the tumor suppressor function of gld-1.