ArticleDevelopmental cell2007
A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to regulate C. elegans sex determination.
Article in Developmental cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 139 citations in OpenAlex.
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- Noncanonical inheritance of phenotypic information by protein amyloids.Nature cell biology · 2024Article
- Evolutionary changes of noncoding elements associated with transition of sexual mode inScience advances · 2024Article
- Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B.Journal of cell science · 2024Article
- Rewiring the Sex-Determination Pathway During the Evolution of Self-Fertility.Molecular biology and evolution · 2024Article
- COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells.Genetics · 2024Article
- Structural insights into the ubiquitylation strategy of the oligomeric CRL2The EMBO journal · 2024Article
- CaMKII mediates sexually dimorphic synaptic transmission at neuromuscular junctions in C. elegans.The Journal of cell biology · 2023Article
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- Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans.Nature communications · 2022Article
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- Sex Determination in Nematode Germ Cells.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2022Review
- Schistosome W-Linked Genes Inform Temporal Dynamics of Sex Chromosome Evolution and Suggest Candidate for Sex Determination.Molecular biology and evolution · 2021Article
- Downregulation of FEM1C enhances metastasis and proliferation in colorectal cancer.Annals of translational medicine · 2021Article
- Transcriptional profiles in Strongyloides stercoralis males reveal deviations from the Caenorhabditis sex determination model.Scientific reports · 2021Article
28 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 2 countries.
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Abstract
In Caenorhabditis elegans, the Gli-family transcription factor TRA-1 is the terminal effector of the sex-determination pathway. TRA-1 activity inhibits male development and allows female fates. Genetic studies have indicated that TRA-1 is negatively regulated by the fem-1, fem-2, and fem-3 genes. However, the mechanism of this regulation has not been understood. Here, we present data that TRA-1 is regulated by degradation mediated by a CUL-2-based ubiquitin ligase complex that contains FEM-1 as the substrate-recognition subunit, and FEM-2 and FEM-3 as cofactors. CUL-2 physically associates with both FEM-1 and TRA-1 in vivo, and cul-2 mutant males share feminization phenotypes with fem mutants. CUL-2 and the FEM proteins negatively regulate TRA-1 protein levels in C. elegans. When expressed in human cells, the FEM proteins interact with human CUL2 and induce the proteasome-dependent degradation of TRA-1. This work demonstrates that the terminal step in C. elegans sex determination is controlled by ubiquitin-mediated proteolysis.
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