Cooperative DNA binding with AP-1 proteins is required for transformation by EWS-Ets fusion proteins

Molecular and Cellular Biology
Sungeun KimRon Wisdom

Abstract

A key molecular event in the genesis of Ewing's sarcoma is the consistent presence of chromosomal translocations that result in the formation of proteins in which the amino terminus of EWS is fused to the carboxyl terminus, including the DNA binding domain, of one of five different Ets family proteins. These fusion proteins function as deregulated transcription factors, resulting in aberrant control of gene expression. Recent data indicate that some EWS-Ets target promoters, including the uridine phosphorylase (UPP) promoter, harbor tandem binding sites for Ets and AP-1 proteins. Here we show that those Ets family proteins that participate in Ewing's sarcoma, including Fli1, ERG, and ETV1, cooperatively bind these tandem elements with Fos-Jun while other Ets family members do not. Analysis of this cooperativity in vitro shows that (i) many different spatial arrangements of the Ets and AP-1 sites support cooperative binding, (ii) the bZIP motifs of Fos and Jun are sufficient to support this cooperativity, and (iii) both the Ets domain and carboxy-terminal sequences of Fli1 are important for cooperative DNA binding. EWS-Fli1 activates the expression of UPP mRNA, is directly bound to the UPP promoter, and transforms 3T3 fibroblast...Continue Reading

References

Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W A MayC T Denny
Apr 1, 1996·Molecular and Cellular Biology·R Janknecht
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·B R PetersonG L Verdine
Aug 26, 1998·Advances in Cancer Research·B J Graves, J M Petersen
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·S l FuP K Vogt
Feb 15, 2001·Oncogene·F O BartelD D Spyropoulos
Jun 19, 2001·The EMBO Journal·M Hassler, T J Richmond
Oct 19, 2001·Oncogene·A Arvand, C T Denny
Jan 10, 2002·Molecular Cell·C W GarvieC Wolberger
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Miles A Pufall, Barbara J Graves
Nov 28, 2002·Molecular Cell·Carlos R EscalanteAneel K Aggarwal
Feb 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maggie C LouieHong-Wu Chen
Oct 1, 2003·Experimental Cell Research·Anikó HevérCraig A Hauser
Oct 23, 2004·Nucleic Acids Research·Peter C HollenhorstBarbara J Graves

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Citations

Oct 21, 2011·Genes & Development·Peter C HollenhorstBarbara J Graves
Sep 19, 2007·Molecular and Cellular Biology·Enrique C TorchiaSuzanne J Baker
Oct 19, 2010·Sarcoma·Patrick P LinGuillermina Lozano
Dec 3, 2011·Sarcoma·David Herrero-MartinDave N T Aryee
Jun 16, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hayriye V ErkizanJeffrey A Toretsky
Aug 19, 2010·Oxidative Medicine and Cellular Longevity·Maqsood M ElahiBashir M Matata
Oct 18, 2008·Expert Review of Anticancer Therapy·Susan Ann Burchill
Aug 30, 2011·Cancer Genetics·Savita Sankar, Stephen L Lessnick
Jan 26, 2007·Cancer Letters·Nicolò Riggi, Ivan Stamenkovic
Jul 1, 2009·Proteomics. Clinical Applications·Juan Madoz-Gúrpide
Sep 27, 2013·Critical Reviews in Biochemistry and Molecular Biology·Adwitiya Kar, Arthur Gutierrez-Hartmann
Apr 29, 2015·Oncogene·P Adamo, M R Ladomery
Jan 25, 2013·ISRN Oncology·Keir A RossJohn G Kennedy
Aug 11, 2007·The Journal of Pathology·N RiggiI Stamenkovic
Feb 6, 2016·Oncotarget·Emily R TheisenStephen L Lessnick
Sep 20, 2011·Cell Cycle·Hayriye V ErkizanJeffrey A Toretsky
Aug 9, 2019·Nucleic Acids Research·Saravana P SelvanathanJeffrey A Toretsky
Apr 25, 2020·Cells·Heinrich KovarBranka Radic-Sarikas
Oct 21, 2020·Nucleic Acids Research·Xianping ShiH Phillip Koeffler
Sep 10, 2009·Cancer Research·José Luis OrdóñezJuan Madoz-Gúrpide
Mar 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Károly SzuhaiPancras C W Hogendoorn
Sep 24, 2015·Disease Models & Mechanisms·Eva KülshammerMirka Uhlirova

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