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Evolutionarily Conserved Multisubunit RBL2/p130 and E2F4 Protein Complex Represses Human Cell Cycle-Dependent Genes in Quiescence

2007; Elsevier BV; Volume: 26; Issue: 4 Linguagem: Inglês

10.1016/j.molcel.2007.04.015

1097-4164

Larisa Litovchick, Subhashini Sadasivam, Laurence Florens, Xiaopeng Zhu, Selene K. Swanson, Vel Murugan, Runsheng Chen, Michael P. Washburn, X. Shirley Liu, James A. DeCaprio,

Cancer-related Molecular Pathways

SummaryThe 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.