Proteasomal ubiquitin receptor RPN-10 controls sex determination in Caenorhabditis elegans
Proteasomal ubiquitin receptor RPN-10 controls sex determination in Caenorhabditis elegans
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DOI：
10.1091/mbc.e06-05-0437
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发表时间：
2006-12-01
影响因子：
3.3
通讯作者：
Kawahara, Hiroyuki
中科院分区：
文献类型：
--
作者：
Shimada, Masumi;Kanematsu, Kenji;Kawahara, Hiroyuki
泛素结合 RPN-10 蛋白充当泛素受体，将客户蛋白递送至 26S 蛋白酶体。尽管泛素识别是蛋白酶体破坏的重要步骤，但酵母中 rpn-10 基因的缺失并不影响活力，表明底物传递途径存在冗余。然而，它们在高等真核生物中的特异性和生物学相关性仍然是个谜。我们在此报道，敲低 rpn-10 基因，而不是任何其他蛋白酶体亚基基因，通过消除秀丽隐杆线虫的雌雄同体精子发生，将雌雄同体性转变为雌性。删除rpn-10基因诱导的女性化表型可以通过敲低tra-2（促进女性发育的性命运决定基因之一）及其下游靶标tra-1来挽救，这表明TRA-2介导的性别决定途径对于Arpn-10诱导的不育表型至关重要。有趣的是，我们发现 rpn-10 和功能相关的泛素连接酶 ufd-2 的共同敲低克服了 fem-3(gf) 的种系肌肉化作用。此外，TRA-2 蛋白在 rpn-10 缺陷的蠕虫中积累。我们的结果表明，RPN-10 介导的泛素通路对于控制 TRA-2 介导的性别决定通路是不可或缺的。
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 Arpn-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.