title: The LIN-15A and LIN-56 transcriptional regulators interact to negatively regulate EGF/Ras signaling in Caenorhabditis elegans vulval cell-fate determination.
abstract: The 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 C(2)CH 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Davison
authors.forename: Adam M
authors.initials: AM
authors.lastname: Saffer
authors.forename: Linda S
authors.initials: LS
authors.lastname: Huang
authors.forename: John
authors.initials: J
authors.lastname: DeModena
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D034622:RNA Interference; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000254:growth & development* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C559280:LIN-56 protein, C elegans; D014157:Transcription Factors; C088818:lin-15A protein, C elegans; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D006655:Histone Deacetylases; D018631:ras Proteins