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PMID:15306688
Citation |
Jäger, S, Schwartz, HT, Horvitz, HR and Conradt, B (2004) The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome. Proc. Natl. Acad. Sci. U.S.A. 101:12549-54 |
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Abstract |
The Caenorhabditis elegans F-box protein SEL-10 and its human homolog have been proposed to regulate LIN-12 Notch signaling by targeting for ubiquitin-mediated proteasomal degradation LIN-12 Notch proteins and SEL-12 PS1 presenilins, the latter of which have been implicated in Alzheimer's disease. We found that sel-10 is the same gene as egl-41, which previously had been defined by gain-of-function mutations that semidominantly cause masculinization of the hermaphrodite soma. Our results demonstrate that mutations causing loss-of-function of sel-10 also have masculinizing activity, indicating that sel-10 functions to promote female development. Genetically, sel-10 acts upstream of the genes fem-1, fem-2, and fem-3 and downstream of her-1 and probably tra-2. When expressed in mammalian cells, SEL-10 protein coimmunoprecipitates with FEM-1, FEM-2, and FEM-3, which are required for masculinization, and FEM-1 and FEM-3 are targeted by SEL-10 for proteasomal degradation. We propose that SEL-10-mediated proteolysis of FEM-1 and FEM-3 is required for normal hermaphrodite development. |
Links |
PubMed PMC515095 Online version:10.1073/pnas.0405087101 |
Keywords |
Animals; Animals, Genetically Modified; Caenorhabditis elegans/genetics; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cysteine Endopeptidases/metabolism; Disorders of Sex Development; Female; Humans; Male; Multienzyme Complexes/metabolism; Mutation; Phenotype; Proteasome Endopeptidase Complex; Sex Determination Processes; Signal Transduction/physiology |
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Significance
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