ABSTRACT In Ewing's sarcoma family tumors, the ets transcription factor gene _FLI1_ is rearranged with one _EWS_ allele resulting in coexpression of germline EWS and chimeric EWS-FLI1

proteins. Here, we investigated the potential of germline EWS, FLI1 and EWS-FLI1 to oligomerize. In two functional _in vivo_ tests, fluorescence resonance energy transfer (FRET) and the

mammalian two-hybrid (MTH) assay, self-association of EWS and EWS-FLI1, but not of FLI1 was detected. In addition, interaction of EWS-FLI1 with EWS and FLI1 was observed. GST pull-down

assays and immunoprecipitation experiments largely confirmed these results. The EWS N-terminal domain present in both EWS and EWS-FLI1 was found to contribute to homotypic and heterotypic

EWS-FLI1 was able to self-associate and also bind to FLI1 via its C-terminal domain, which comprises the FLI1 DNA-binding motif. Accordingly, the EWS-FLI1 interaction was not disrupted by

RNaseA treatment. Despite its potential to oligomerize, EWS-FLI1 bound to a tandem ets-binding site of the TGF_β_ type II receptor promoter as a monomer. Therefore, the functional

consequences of homo- and hetero-oligomerization of EWS and EWS-FLI1 proteins remain to be elucidated. Access through your institution Buy or subscribe This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE FLI PORTION OF EWS/FLI CONTRIBUTES A

TRANSCRIPTIONAL REGULATORY FUNCTION THAT IS DISTINCT AND SEPARABLE FROM ITS DNA-BINDING FUNCTION IN EWING SARCOMA Article Open access 18 June 2021 ETV6 DEPENDENCY IN EWING SARCOMA BY

ANTAGONISM OF EWS-FLI1-MEDIATED ENHANCER ACTIVATION Article 19 January 2023 DIMERIZATION OF THE 4IG ISOFORM OF B7-H3 IN TUMOR CELLS MEDIATES ENHANCED PROLIFERATION AND TUMORIGENIC SIGNALING

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_Oncogene_, 20, 626–633. Download references ACKNOWLEDGEMENTS This study was supported in part by Grants 13708GEN and 14299GEN of the Austrian Science Fund. AUTHOR INFORMATION Author notes

* Laura Spahn and Christine Siligan: These authors contributed equally AUTHORS AND AFFILIATIONS * Children's Cancer Research Institute, St Anna Kinderspital, Vienna, A-1090, Austria

Laura Spahn, Christine Siligan, Radostina Bachmaier, Dave N T Aryee & Heinrich Kovar * Department of Vascular Biology and Thrombosis Research, University of Vienna, and Competence Center

‘Bio-Molecular Therapeutics’, Vienna, 1235, Austria Johannes A Schmid Authors * Laura Spahn View author publications You can also search for this author inPubMed Google Scholar * Christine

Siligan View author publications You can also search for this author inPubMed Google Scholar * Radostina Bachmaier View author publications You can also search for this author inPubMed 

Google Scholar * Johannes A Schmid View author publications You can also search for this author inPubMed Google Scholar * Dave N T Aryee View author publications You can also search for this

author inPubMed Google Scholar * Heinrich Kovar View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Heinrich Kovar.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Spahn, L., Siligan, C., Bachmaier, R. _et al._ Homotypic and heterotypic interactions of EWS, FLI1 and

their oncogenic fusion protein. _Oncogene_ 22, 6819–6829 (2003). https://doi.org/10.1038/sj.onc.1206810 Download citation * Received: 26 March 2003 * Revised: 08 May 2003 * Accepted: 15 May

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KEYWORDS * EWS * FLI1 * Ewing's sarcoma * dimerization * protein interaction