FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C-elegans hermaphrodite germline

Male sex determination in the Caenorhabditis elegans hermaphrodite germline requires translational repression of tra-2 mRNA by the GLD-1 RNA binding p rotein. We cloned fog-2 by finding that its gene product physically interac ts with GLD-1, forming a FOG-2/GLD-1/tra-2 3'untranslated region ternary co mplex. FOG-2 has an N-terminal F-box and a novel C-terminal domain called F TH, Canonical F-box proteins act as bridging components of the SCF ubiquiti n ligase complex; the N-terminal F-box binds a Skp1 homolog, recruiting ubi quination machinery, while a C-terminal protein-protein interaction domain binds a specific substrate for degradation. However, since both fog-2 and g ld-1 are necessary for spermatogenesis, FOG-2 cannot target GLD-1 for ubiqu itin-mediated degradation. We propose that FOG-2 also acts as a bridge, bri nging GLD-1 bound to tra-2 mRNA into a multiprotein translational repressio n complex, thus representing a novel function for an F-box protein. fog-2 i s a member of a large, apparently rapidly evolving, C. elegans gene family that has expanded, in part, by local duplications; fog-2 related genes have not been found outside nematodes. fog-2 may have arisen during evolution o f self-fertile hermaphroditism from an ancestral female/male species.