The LIN-15A and LIN-56 Transcriptional Regulators Interact to Negatively Regulate EGF/Ras Signaling inCaenorhabditis elegansVulval Cell-Fate Determination
The LIN-15A and LIN-56 Transcriptional Regulators Interact to Negatively Regulate EGF/Ras Signaling inCaenorhabditis elegansVulval Cell-Fate Determination
AbstractThe restricted expression of epidermal growth factor (EGF) family ligands is important for proper development and for preventing cancerous growth in mammals. In Caenorhabditis elegans, the class A and B synthetic multivulva (synMuv) genes redundantly repress expression of lin-3 EGF to negatively regulate Ras-mediated vulval development. The class B synMuv genes encode proteins homologous to components of the NuRD and Myb-MuvB/dREAM transcriptional repressor complexes, indicating that they likely silence lin-3 EGF through chromatin remodeling. The two class A synMuv genes cloned thus far, lin-8 and lin-15A, both encode novel proteins. The LIN-8 protein is nuclear. We have characterized the class A synMuv gene lin-56 and found it to encode a novel protein that shares a THAP-like C2CH motif with LIN-15A. Both the LIN-56 and LIN-15A proteins localize to nuclei. Wild-type levels of LIN-56 require LIN-15A, and wild-type levels and/or localization of LIN-15A requires LIN-56. Furthermore, LIN-56 and LIN-15A interact in the yeast two-hybrid system. We propose that LIN-56 and LIN-15A associate in a nuclear complex that inhibits vulval specification by repressing lin-3 EGF expression.
- Howard Hughes Medical Institute United States
- California Institute of Technology United States
- Massachusetts Institute of Technology United States
570, Epidermal Growth Factor, Molecular Sequence Data, Histone Deacetylases, Vulva, Animals, Genetically Modified, Gene Expression Regulation, ras Proteins, Animals, Female, RNA Interference, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Signal Transduction, Transcription Factors
570, Epidermal Growth Factor, Molecular Sequence Data, Histone Deacetylases, Vulva, Animals, Genetically Modified, Gene Expression Regulation, ras Proteins, Animals, Female, RNA Interference, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Signal Transduction, Transcription Factors
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