ArticleNature cell biology2015
Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.
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Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 74 citations in OpenAlex.
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Authors and funding
19 authors at 2 institutions in 1 country.
Huayang Liu1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Xing Tang1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Arunima Srivastava1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Thierry Pécot1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Piotr Daniel1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Benjamin Hemmelgarn1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Stephan Reyes1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Nicholas Fackler1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Amneet Bajwa1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Raleigh Kladney1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Christopher Koivisto1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Zhong ChenDepartment of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Qianben WangDepartment of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Kun HuangDepartment of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210, USA.
Raghu MachirajuDepartment of Computer Science and Engineering, The Ohio State University, Columbus, Ohio 43210, USA.
Maria Teresa Sáenz-RoblesDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Paul CantalupoDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
James M PipasDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Gustavo Leone1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
The Ohio State University · USUniversity of Pittsburgh · US
Funding
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8MSuppression of Mammary Tumorigenesis by Stromal p53P01CA097189 · NCI · OHIO STATE UNIVERSITY · PI FERNANDEZ, SOLEDAD A · 2004 to 2016
$16.1MExpression of Simian Virus 40 T antigens in IntestineR01CA098956 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PIPAS, JAMES M · 2003 to 2013
$3.2MTumor Suppressor Roles of E2F7 & E2F8 in Hepatocellular Carcinoma (HCC)R01CA121275 · NCI · OHIO STATE UNIVERSITY · PI LEONE, GUSTAVO WALTER · 2008 to 2018
$3.1ME2F3 and embryonic developmentR01HD047470 · NICHD · OHIO STATE UNIVERSITY · PI LEONE, GUSTAVO WALTER · 2004 to 2008
$1.6MNCATS NIH HHS UL1 TR000005NCI NIH HHS P01 CA097189NCI NIH HHS R01 CA098956NCI NIH HHS R01CA098956NCI NIH HHS R01 CA121275NCI NIH HHS R01CA121275NICHD NIH HHS R01 HD047470NICHD NIH HHS R01HD047470
Abstract
Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1-3 have little impact on normal G1-S transitions. Instead, they synergistically control an S-G2 transcriptional program required for normal cell divisions and maintaining crypt-villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the 'super activation' of a G1-S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S-G2 program essential for normal cell cycles to a G1-S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.
Indexed as
Cell Cycle CheckpointsCell ProliferationAnimalsBinding SitesChromatin Assembly and DisassemblyE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorE2F Transcription FactorsEpithelial CellsFemaleG1 Phase Cell Cycle CheckpointsG2 Phase Cell Cycle CheckpointsGene Expression RegulationGenotypeIntestine, SmallE2f1 protein, mouseE2F1 Transcription FactorE2f2 protein, mouseE2F2 Transcription FactorE2f3 protein, mouseE2F3 Transcription FactorE2F Transcription FactorsMyc protein, mouseProto-Oncogene Proteins c-mycRetinoblastoma Protein
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