Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence

Mol Cell. 2007 May 25;26(4):539-51. doi: 10.1016/j.molcel.2007.04.015.


The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cell Cycle / physiology*
  • Cellular Senescence / physiology*
  • Conserved Sequence
  • Crk-Associated Substrate Protein / genetics*
  • Crk-Associated Substrate Protein / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • E2F4 Transcription Factor / genetics*
  • E2F4 Transcription Factor / metabolism
  • Evolution, Molecular*
  • Gene Deletion
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kv Channel-Interacting Proteins / genetics
  • Mutation
  • Neoplasms / genetics
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Proteome
  • Repressor Proteins / genetics
  • Retinoblastoma Protein / genetics
  • Retinoblastoma-Like Protein p130 / genetics*
  • Retinoblastoma-Like Protein p130 / metabolism
  • Suppression, Genetic


  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • E2F4 Transcription Factor
  • E2F4 protein, human
  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • Protein Subunits
  • Proteome
  • RBL2 protein, human
  • Repressor Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Like Protein p130

Associated data

  • GEO/GSE7516