title: Proteasomal ubiquitin receptor RPN-10 controls sex determination in Caenorhabditis elegans.
abstract: 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 Delta rpn-10-induced sterile phenotype. Intriguingly, we found that co-knockdown 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.
authors.affiliation: Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanematsu
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Yokosawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahara
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D005262:Feminization; D017353:Gene Deletion; D007246:Infertility; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D019849:Sex Determination Processes; D013091:Spermatogenesis / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D050505:Mutant Proteins; C516341:RPN-10 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; C075059:fem-3 protein, C elegans; C076107:tra-2 protein, C elegans; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease