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PMID: 15306688 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 34 ·2004-08-24 ·Pages 12549-54

Jäger S, Schwartz HT, Horvitz HR, Conradt B

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.

MeSH Terms
Animals Animals, Genetically Modified Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins/genetics,metabolism Cell Cycle Proteins/genetics,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
Chemicals
Caenorhabditis elegans Proteins Cell Cycle Proteins FEM-1 protein, C elegans Multienzyme Complexes SEL-10 protein, C elegans fem-3 protein, C elegans Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jäger Sibylle
Max Planck Institute of Neurobiology, Am Klopferspitz 18a, D-82152 Planegg-Martinsried, Germany.
Schwartz Hillel T
Horvitz H Robert
Conradt Barbara
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0405087101
Published
2004-08-24
Epub
2004-00-11
Pages
12549-54
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC515095
Subset
IM
Grants
NIGMS NIH HHS · R01 GM024663 · United States
NIGMS NIH HHS · R37 GM024663 · United States
NIGMS NIH HHS · GM 24663 · United States
External Links
PubMed source DOI: 10.1073/pnas.0405087101 PMC Full Text View journal details
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