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.
Litovchick
Larisa
L
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.
Sadasivam
Subhashini
S
Florens
Laurence
L
Zhu
Xiaopeng
X
Swanson
Selene K
SK
Velmurugan
Soundarapandian
S
Chen
Runsheng
R
Washburn
Michael P
MP
Liu
X Shirley
XS
DeCaprio
James A
JA
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
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