Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.
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.
Mesh Terms:
Animals, Caenorhabditis elegans, Cell Aging, Cell Cycle, Conserved Sequence, Crk-Associated Substrate Protein, Drosophila melanogaster, E2F4 Transcription Factor, Evolution, Molecular, Gene Deletion, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Humans, Kv Channel-Interacting Proteins, Mutation, Neoplasms, Protein Subunits, Proteome, Repressor Proteins, Retinoblastoma Protein, Retinoblastoma-Like Protein p130, Suppression, Genetic
Animals, Caenorhabditis elegans, Cell Aging, Cell Cycle, Conserved Sequence, Crk-Associated Substrate Protein, Drosophila melanogaster, E2F4 Transcription Factor, Evolution, Molecular, Gene Deletion, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Humans, Kv Channel-Interacting Proteins, Mutation, Neoplasms, Protein Subunits, Proteome, Repressor Proteins, Retinoblastoma Protein, Retinoblastoma-Like Protein p130, Suppression, Genetic
Mol. Cell
Date: May. 25, 2007
PubMed ID: 17531812
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