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Journal article
Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression
Nature communications, v 6(1), pp 10028-10028
01 Dec 2015
PMID: 26639898
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Changes in gene expression during tumorigenesis are often considered the consequence of de novo mutations occurring in the tumour. An alternative possibility is that the transcriptional response of oncogenic transcription factors evolves during tumorigenesis. Here we show that aberrant E2f activity, following inactivation of the Rb gene family in a mouse model of liver cancer, initially activates a robust gene expression programme associated with the cell cycle. Slowly accumulating E2f1 progressively recruits a Pontin/Reptin complex to open the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response. This mechanism enhances the E2f-mediated transactivation of cell cycle genes and initiates the activation of low binding affinity E2f target genes that regulate non-cell-cycle functions, such as the Warburg effect. These data indicate that both the physiological and the oncogenic activities of E2f result in distinct transcriptional responses, which could be exploited to target E2f oncogenic activity for therapy.
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Details
- Title
- Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression
- Creators
- Amy Tarangelo - Children's Hospital of PhiladelphiaNathanael Lo - Children's Hospital of PhiladelphiaRebecca Teng - Children's Hospital of PhiladelphiaEunsun Kim - Children's Hospital of PhiladelphiaLinh Le - Children's Hospital of PhiladelphiaDeborah Watson - Children's Hospital of PhiladelphiaEmma E. Furth - University of PennsylvaniaPichai Raman - Children's Hospital of PhiladelphiaUrsula Ehmer - Department of Medicine, University Hospital of Munich, Munich 81675, Germany.Patrick Viatour - University of PennsylvaniaEdward Kim - Computer Science (Computing)
- Publication Details
- Nature communications, v 6(1), pp 10028-10028
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- Center for Childhood Cancer Research at CHOP SU2C Foundation Alex Lemonade Stand Foundation Canuso Foundation W.W. Smith Charitable Trust Fund
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Computer Science
- Web of Science ID
- WOS:000367567500003
- Scopus ID
- 2-s2.0-84949520568
- Other Identifier
- 991019173535804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology