The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome.
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.
Jäger
Sibylle
S
Max Planck Institute of Neurobiology, Am Klopferspitz 18a, D-82152 Planegg-Martinsried, Germany.
Schwartz
Hillel T
HT
Horvitz
H Robert
HR
Conradt
Barbara
B
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D012734:Disorders of Sex Development; D005260:Female; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex; D019849:Sex Determination Processes; D015398:Signal Transduction / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C115306:FEM-1 protein, C elegans; D009097:Multienzyme Complexes; C109554:SEL-10 protein, C elegans; C075059:fem-3 protein, C elegans; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex