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MBC in Press, published online ahead of print October 18, 2006
Mol. Biol. Cell 10.1091/mbc.E06-05-0437

A more recent version of this article appeared on December 1, 2006
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Submitted on May 22, 2006
Revised on September 6, 2006
Accepted on October 6, 2006

Proteasomal Ubiquitin Receptor RPN-10 Controls Sex Determination in Caenorhabditis elegans

Masumi Shimada,* Kenji Kanematsu,* Keiji Tanaka,{dagger} Hideyoshi Yokosawa,* and Hiroyuki Kawahara*

*Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; {dagger}Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Sciences, Tokyo 113-8613, Japan

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 {Delta}rpn-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.

Address correspondence to: Hiroyuki Kawahara (kawahara{at}pharm.hokudai.ac.jp)




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J. Hamazaki, K. Sasaki, H. Kawahara, S.-i. Hisanaga, K. Tanaka, and S. Murata
Rpn10-Mediated Degradation of Ubiquitinated Proteins Is Essential for Mouse Development
Mol. Cell. Biol., October 1, 2007; 27(19): 6629 - 6638.
[Abstract] [Full Text] [PDF]


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