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Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence 总被引:2,自引:0,他引:2
Litovchick L Sadasivam S Florens L Zhu X Swanson SK Velmurugan S Chen R Washburn MP Liu XS DeCaprio JA 《Molecular cell》2007,26(4):539-551
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. 相似文献
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Eriko Iwata Norihito Nakamichi Takamasa Suzuki Poyu Chen Misato Ohtani Takashi Ishida Hanako Hosoya Sabine Müller Tünde Leviczky Aladár Pettkó‐Szandtner Zsuzsanna Darula Akitoshi Iwamoto Mika Nomoto Yasuomi Tada Tetsuya Higashiyama Taku Demura John H Doonan Marie‐Theres Hauser Keiko Sugimoto Masaaki Umeda Zoltán Magyar László Bögre Masaki Ito 《The EMBO journal》2015,34(15):1992-2007
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Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR-bound and RBR-free complexes 总被引:1,自引:0,他引:1
Magyar Z Horváth B Khan S Mohammed B Henriques R De Veylder L Bakó L Scheres B Bögre L 《The EMBO journal》2012,31(6):1480-1493
Post-embryonic growth in plants depends on the continuous supply of undifferentiated cells within meristems. Proliferating cells maintain their competence for division by active repression of differentiation and the associated endocycle entry. We show by upregulation and downregulation of E2FA that it is required for maintaining proliferation, as well as for endocycle entry. While E2FB-RBR1 (retinoblastoma-related protein 1) complexes are reduced after sucrose addition or at elevated CYCD3;1 levels, E2FA maintains a stable complex with RBR1 in proliferating cells. Chromatin immunoprecipitation shows that RBR1 binds in the proximity of E2F promoter elements in CCS52A1 and CSS52A2 genes, central regulators for the switch from proliferation to endocycles. Overexpression of a truncated E2FA mutant (E2FA(ΔRB)) lacking the RBR1-binding domain interferes with RBR1 recruitment to promoters through E2FA, leading to decreased meristem size in roots, premature cell expansion and hyperactivated endocycle in leaves. E2F target genes, including CCS52A1 and CCS52A2, are upregulated in E2FA(ΔRB) and e2fa knockout lines. These data suggest that E2FA in complex with RBR1 forms a repressor complex in proliferating cells to inhibit premature differentiation and endocycle entry. Thus, E2FA regulates organ growth via two distinct, sequentially operating pathways. 相似文献
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RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest 总被引:7,自引:0,他引:7 下载免费PDF全文
Lai A Kennedy BK Barbie DA Bertos NR Yang XJ Theberge MC Tsai SC Seto E Zhang Y Kuzmichev A Lane WS Reinberg D Harlow E Branton PE 《Molecular and cellular biology》2001,21(8):2918-2932
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Olson BJ Oberholzer M Li Y Zones JM Kohli HS Bisova K Fang SC Meisenhelder J Hunter T Umen JG 《The Plant cell》2010,22(10):3331-3347
We examined the cell cycle dynamics of the retinoblastoma (RB) protein complex in the unicellular alga Chlamydomonas reinhardtii that has single homologs for each subunit-RB, E2F, and DP. We found that Chlamydomonas RB (encoded by MAT3) is a cell cycle-regulated phosphoprotein, that E2F1-DP1 can bind to a consensus E2F site, and that all three proteins interact in vivo to form a complex that can be quantitatively immunopurified. Yeast two-hybrid assays revealed the formation of a ternary complex between MAT3, DP1, and E2F1 that requires a C-terminal motif in E2F1 analogous to the RB binding domain of plant and animal E2Fs. We examined the abundance of MAT3/RB and E2F1-DP1 in highly synchronous cultures and found that they are synthesized and remain stably associated throughout the cell cycle with no detectable fraction of free E2F1-DP1. Consistent with their stable association, MAT3/RB and DP1 are constitutively nuclear, and MAT3/RB does not require DP1-E2F1 for nuclear localization. In the nucleus, MAT3/RB remains bound to chromatin throughout the cell cycle, and its chromatin binding is mediated through E2F1-DP1. Together, our data show that E2F-DP complexes can regulate the cell cycle without dissociation of their RB-related subunit and that other changes may be sufficient to convert RB-E2F-DP from a cell cycle repressor to an activator. 相似文献
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