High impact information on gld-1

• An independent ENU-induced mutation has a nonconservative amino acid change in one of two newly identified domains that are conserved from the C. elegans gld-1 tumour suppressor gene to the human Src-associated protein Sam68 [1].
• We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle [2].
• The gld-1 gene of Caenorhabditis elegans is a germ-line-specific tumor suppressor gene that is essential for oogenesis [3].
• 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 [3].
• These include missense mutations in an absolutely conserved residue of the KH domain that eliminate the tumor suppressor function of gld-1 [3].

Biological context of gld-1

• However, since both fog-2 and gld-1 are necessary for spermatogenesis, FOG-2 cannot target GLD-1 for ubiquitin-mediated degradation [4].
• In addition, C. briggsae gld-1 appears to play the opposite role in sex determination (promoting the female fate) while maintaining conserved roles in meiotic progression during oogenesis [5].
• First, the activation of gld-1 mRNA by GLD-2 identifies a positive regulatory step that reinforces the decision to enter the meiotic cell cycle [6].
• Therefore, a molecular switch regulates gld-1 mRNA activity to accomplish the transition from mitosis to meiosis [6].
• Here we report that the gld-1 mRNA is a direct target of the GLD-2 poly(A) polymerase: polyadenylation of gld-1 mRNA depends on GLD-2, the abundance of GLD-1 protein is dependent on GLD-2, and the gld-1 mRNA coimmunoprecipitates with both GLD-2 and GLD-3 proteins [6].

Anatomical context of gld-1

• The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line [6].
• Second, gld-1 mRNA is initially repressed by FBF (for fem-3 binding factor) to maintain stem cells but then becomes activated by the GLD-2 poly(A) polymerase once stem cells begin to make the transition into the meiotic cell cycle [6].
• Here we demonstrate that gld-1(null) germ lines express female-specific, but not male-specific, molecular markers, indicating that gld-1 acts downstream of sexual fate specification to regulate oocyte differentiation [7].

Regulatory relationships of gld-1

• Therefore, we hypothesize that glp-1 promotes proliferation by inhibiting the meiosis-promoting functions of gld-1 and gld-2 [8].

Other interactions of gld-1

• With respect to this second function, gld-2 appears to be functionally redundant with a previously described gene, gld-1 (Francis, R., Barton, M. K., Kimble, J. and Schedl, T. (1995) Genetics 139, 579-606) [8].
• Epistasis analyses show that gld-1 and gld-2 work downstream of the glp-1 signal transduction pathway [8].
• The distribution of MES-3 in the adult germline is regulated by the translational repressor GLD-1: MES-3 is absent from the region of the germline where GLD-1 is known to be present, MES-3 is overexpressed in the germline of gld-1 mutants, and GLD-1 specifically binds the mes-3 3' untranslated region (3' UTR) [9].
• The long life spans of daf-2/insulin-receptor mutants were not shortened at all by gld-1 mutations; we attribute this finding to decreased cell division and increased DAF-16/p53-dependent apoptosis within the tumors [10].

References