title: dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development.
abstract: The synthetic multivulva (synMuv) genes define two functionally redundant pathways that antagonize RTK/Ras signaling during Caenorhabditis elegans vulval induction. The synMuv gene lin-35 encodes a protein similar to the mammalian tumor suppressor pRB and has been proposed to act as a transcriptional repressor. Studies using mammalian cells have shown that pRB can prevent cell cycle progression by inhibiting DP/E2F-mediated transcriptional activation. We identified C. elegans genes that encode proteins similar to DP or E2F. Loss-of-function mutations in two of these genes, dpl-1 DP and efl-1 E2F, caused the same vulval abnormalities as do lin-35 Rb loss-of-function mutations. We propose that rather than being inhibited by lin-35 Rb, dpl-1 DP and efl-1 E2F act with lin-35 Rb in transcriptional repression to antagonize RTK/Ras signaling during vulval development.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ceol
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D009687:Nuclear Proteins; D010641:Phenotype; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C470734:EFF-1 protein, C elegans; C512897:ELF1 protein, human; C512896:Elf1 protein, mouse; D015801:Helminth Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C433249:dpl-1 protein, C elegans; C493765:efl-1 protein, C elegans; C116485:lin-35 protein, C elegans; D018631:ras Proteins