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Evolutionarily Conserved Multisubunit RBL2/p130 and E2F4 Protein Complex Represses Human Cell Cycle-Dependent Genes in Quiescence
Open accessAbstract
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.
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“The pocket proteins p107 and p130, together with E2F4, are members of the multiprotein repressor complex DREAM that binds cell cycle genes during quiescence.104, 105, 106”
From Census and evaluation of p53 target genes (2017) · cites this paper as [104]
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Metadata
- Authors
- Litovchick, L., Sadasivam, S., Florens, L., Zhu, X., Swanson, S. K., Velmurugan, S., Chen, R., Washburn, M. P., Liu, X. S., & DeCaprio, J. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Stowers Institute for Medical Research (US)
- Chinese Academy of Sciences (CN)
- Harvard University (US)
- Corresponding author
- DeCaprio, James A.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 26
- Issue
- 4
- Pages
- 539-551
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2156397151
- Cited by
- 396
- References
- 39
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 17 · 2023: 16 · 2022: 28 · 2021: 31 · 2020: 24 · 2019: 17 · 2018: 17 · 2017: 23 · 2016: 21 · 2015: 14 · 2014: 17 · 2013: 26 · 2012: 34
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2269 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (HG004069-01, PO1 CA50661, RO1 CA063113)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- E2F4, DREAM complex, retinoblastoma protein family, cell cycle-dependent gene expression, quiescence, G0 phase, Drosophila melanogaster, Caenorhabditis elegans, promoter binding
- MeSH terms
- Animals, Cell Cycle, Drosophila melanogaster, Gene Expression Regulation, Humans, Mutation, Neoplasms, Repressor Proteins, Suppression, Genetic, Gene Expression Regulation, Neoplastic, Retinoblastoma Protein, Cellular Senescence, Conserved Sequence, Caenorhabditis elegans, Gene Deletion, Evolution, Molecular, Proteome, Protein Subunits, E2F4 Transcription Factor, Retinoblastoma-Like Protein p130, Crk-Associated Substrate Protein, Kv Channel-Interacting Proteins
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