title: Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Litovchick
authors.forename: Subhashini
authors.initials: S
authors.lastname: Sadasivam
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Velmurugan
authors.forename: Runsheng
authors.initials: R
authors.lastname: Chen
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D017124:Conserved Sequence; D050719:Crk-Associated Substrate Protein / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D050704:E2F4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D020543:Proteome; D012097:Repressor Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics* / Q000378:metabolism; D013489:Suppression, Genetic
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D021122:Protein Subunits; D020543:Proteome; C493837:RBL2 protein, human; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130