Monitoring Editor: Thomas Sommer The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome. Although ubiquitin recognition is an essential step for proteasomal destruction, deletion of the
rpn-10 gene in yeast does not influence viability, indicating redundancy of the substrate delivery pathway. However, their specificity and biological relevance in higher eukaryotes is still enigmatic. We report herein that knockdown of the
rpn-10 gene, but not any other proteasome subunit genes, sexually transforms hermaphrodites to females by eliminating hermaphrodite spermatogenesis in Caenorhabditis elegans. The feminization phenotype induced by deletion of the
rpn-10 gene was rescued by knockdown of
tra-2, one of sexual fate decision genes promoting female development, and its downstream target
tra-1, indicating that the TRA-2-mediated sex-determination pathway is crucial for the Deltarpn-10-induced sterile phenotype. Intriguingly, we found that coknockdown of
rpn-10 and functionally related ubiquitin ligase
ufd-2 overcomes the germline musculinizing effect of
fem-3(gf). Furthermore, TRA-2 proteins accumulated in
rpn-10-defective worms. Our results show that the RPN-10-mediated ubiquitin pathway is indispensable for control of the TRA-2-mediated sex-determining pathway.