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PMID:17609115
| Citation |
Starostina, NG, Lim, JM, Schvarzstein, M, Wells, L, Spence, AM and Kipreos, ET (2007) A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to regulate C. elegans sex determination. Dev. Cell 13:127-39 |
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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. |
| Links |
PubMed PMC2064902 Online version:10.1016/j.devcel.2007.05.008 |
| Keywords |
Amino Acid Sequence; Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/growth & development; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Cycle Proteins/metabolism; Cullin Proteins/chemistry; Cullin Proteins/genetics; Cullin Proteins/metabolism; DNA-Binding Proteins/metabolism; Disorders of Sex Development; Molecular Sequence Data; Mutation; Phenotype; Phosphoprotein Phosphatases/metabolism; Proteasome Endopeptidase Complex/metabolism; Sex Determination Processes; Substrate Specificity; Transcription Factors/metabolism; Ubiquitin/metabolism; Ubiquitin-Protein Ligase Complexes/metabolism; Ubiquitin-Protein Ligases/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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