Epigenetic factor EPC1 is a master regulator of DNA damage response by interacting with E2F1 to silence death and activate metastasis-related gene signatures

Nucleic Acids Research
Yajie WangDavid Engelmann

Abstract

Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Recently, it has been shown that aberrant E2F1 expression often detectable in advanced cancers contributes essentially to cancer cell propagation and characterizes the aggressive potential of a tumor. Conceptually, this requires a subset of malignant cells capable of evading apoptotic death through anticancer drugs. The molecular mechanism by which the pro-apoptotic activity of E2F1 is antagonized is widely unclear. Here we report a novel function for EPC1 (enhancer of polycomb homolog 1) in DNA damage protection. Depletion of EPC1 potentiates E2F1-mediated apoptosis in response to genotoxic treatment and abolishes tumor cell motility. We found that E2F1 directly binds to the EPC1 promoter and EPC1 vice versa physically interacts with bifunctional E2F1 to modulate its transcriptional activity in a target gene-specific manner. Remarkably, nuclear-colocalized EPC1 activates E2F1 to upregulate the expression of anti-apoptotic survival genes such as BCL-2 or Survivin/BIRC5 and inhibits death-inducing targets. The uncovered cooperativity between EPC1 and E2F1 triggers a metastasis-related gene signature in advanced cancers that predicts poor patient su...Continue Reading

References

Jan 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·P H HayesR E Denell
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·M VidalE Harlow
Dec 2, 2000·Nature Genetics·T Stiewe, B M Pützer
Apr 9, 2002·Nucleic Acids Research·Jens StanelleBrigitte M Pützer
Jun 26, 2002·Neoplasia : an International Journal for Oncology Research·Young-Goo LeeKenneth J Pienta
Oct 11, 2002·Nature·Sooryanarayana VaramballyArul M Chinnaiyan
Mar 12, 2003·Cell·Valerio Orlando
May 27, 2003·Nature Cell Biology·Natalia PediconiMassimo Levrero
Jun 5, 2003·Proteins·Rong ChenZhiping Weng
Sep 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Timothy C Hallstrom, Joseph R Nevins
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
Oct 7, 2003·EMBO Reports·Gaëlle Legube, Didier Trouche
Oct 28, 2003·Proteins·Li LiZhiping Weng
Feb 18, 2004·Molecular and Cellular Biology·Yannick DoyonJacques Côté
Sep 1, 2004·Trends in Biochemical Sciences·Stuart S LevineRobert E Kingston
Nov 30, 2004·Science·Nicole J FrancisChristopher L Woodcock
May 5, 2005·Molecular and Cellular Biology·Kaoru MurataNagahiro Minato
Aug 18, 2005·International Journal of Hematology·Masashi SawaTomoki Naoe
Feb 17, 2006·Genes & Development·Timothy C Hallstrom, Joseph R Nevins
Mar 15, 2006·Trends in Molecular Medicine·Jens Stanelle, Brigitte M Pützer
Apr 4, 2006·Nucleic Acids Research·Katrin NowakWerner Lutz
Aug 21, 2007·The Journal of Biological Chemistry·Chuangui WangJiandong Chen
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Sep 23, 2008·Trends in Cell Biology·Shirley Polager, Doron Ginsberg
Oct 9, 2008·The Journal of Biological Chemistry·Tomás RacekBrigitte M Pützer
Feb 13, 2009·Molecular Biology of the Cell·Petra ObexerMichael Ausserlechner
Apr 11, 2009·The Journal of Biological Chemistry·Ju-Ryoung KimHyun Kook
Oct 24, 2009·Nature Reviews. Cancer·Adrian P Bracken, Kristian Helin
Dec 17, 2009·Cellular and Molecular Life Sciences : CMLS·David EngelmannBrigitte M Pützer
Dec 23, 2009·Journal of the National Cancer Institute·Vijay AllaBrigitte M Pützer

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Citations

Feb 18, 2017·Cell Death and Differentiation·Igor ShatsLingchong You
Jul 28, 2016·Biochimica Et Biophysica Acta·Suchi SmitaRüdiger Köhling
Sep 9, 2017·Current Genetics·Naomi E Searle, Lorraine Pillus
May 15, 2018·Frontiers in Immunology·Johanna Meier-SoelchMichael Kracht
Aug 24, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jiafei LiuChengchao Shou

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