dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development

Mol Cell. 2001 Mar;7(3):461-73. doi: 10.1016/s1097-2765(01)00194-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins*
  • Cell Cycle Proteins*
  • Cell Division
  • Cell Lineage
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • E2F Transcription Factors
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Genes, Helminth / genetics
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Membrane Glycoproteins
  • Molecular Sequence Data
  • Neurons / cytology
  • Nuclear Proteins
  • Phenotype
  • Protein Binding
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vulva / cytology
  • Vulva / embryology*
  • Vulva / metabolism
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • EFF-1 protein, C elegans
  • ELF1 protein, human
  • Elf1 protein, mouse
  • Helminth Proteins
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • dpl-1 protein, C elegans
  • efl-1 protein, C elegans
  • lin-35 protein, C elegans
  • ras Proteins

Associated data

  • GENBANK/AY028165
  • GENBANK/AY028166
  • GENBANK/AY028167