LINC, a Human Complex That is Related to pRB-Containing Complexes in Invertebrates Regulates the Expression of G2/M Genes
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Here we report the identification of the LIN complex (LINC), a human multiprotein complex that is required for transcriptional activation of G2/M genes. LINC is related to the recently identified dREAM and DRM complexes of Drosophila and C. elegans that contain homologs of the mammalian retinoblastoma tumor suppressor protein. The LINC core complex consists of at least five subunits including the chromatin-associated LIN-9 and RbAp48 proteins. LINC dynamically associates with pocket proteins, E2F and B-MYB during the cell cycle. In quiescent cells, LINC binds to p130 and E2F4. During cell cycle entry, E2F4 and p130 dissociate and LINC switches to B-MYB and p107. Chromatin Immunoprecipitation experiments demonstrate that LINC associates with a large number of E2F-regulated promoters in quiescent cells. However, RNAi experiments reveal that LINC is not required for repression. In S-phase, LINC selectively binds to the promoters of G2/M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation.
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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.
“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 [105]
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El‐Sharnouby, S., Redhouse, J. L., & White, R. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003842 · Cited by 24 · see citing works
Insights from the protein interaction Universe of the multifunctional “Goldilocks” kinase DYRK1A
Ananthapadmanabhan, V., Shows, K. H., DICKINSON, A. J. G., & Litovchick, L. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1277537 · Cited by 23 · see citing works
Drosophila RB Proteins Repress Differentiation-Specific Genes via Two Different Mechanisms
Lee, H., Ohno, K., Voskoboynik, Y., Ragusano, L., Martinez, A., & Dimova, D. K. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01075-09 · Cited by 23 · see citing works
- Authors
- Schmit, F., Korenjak, M., Mannefeld, M., Schmitt, K., Franke, C., von Eyss, B., Gagrica, S., Hanel, F., Brehm, A., & Gaubatz, S.
- Affiliations
- University of Würzburg (DE)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2007-08
- Volume
- 6
- Issue
- 15
- Pages
- 1903-1913
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2016783637
- Cited by
- 179
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 15 · 2020: 11 · 2019: 10 · 2018: 10 · 2017: 12 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 17 · 2012: 15
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell Cycle (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- 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
- LINC complex, RbAp48, retinoblastoma protein, transcriptional activation, E2F4, p130, B-Myb, p107, pocket proteins, cell cycle regulation, chromatin binding, DREAM complex, mitosis
- MeSH terms
- Animals, Cell Line, Drosophila melanogaster, Gene Expression Regulation, Humans, Mitosis, Nerve Tissue Proteins, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Trans-Activators, Retinoblastoma Protein, G2 Phase, Caenorhabditis elegans, Protein Subunits, Tumor Suppressor Proteins, RNA Interference, E2F Transcription Factors
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