Abstract
Ets proteins constitute a family of conserved sequence-specific DNA-binding proteins and function as transcription factors. ETS1 plays important roles in differentiation, lymphoid cell development, invasiveness and angiogenesis. Such diverse roles of ETS1 are likely to be dependent on its associated proteins. A yeast two-hybrid screen was conducted and here we describe a novel ETS1 interacting protein designated as ETS1-associated protein II (EAPII). EAPII protein interacts with ETS1 and other Ets proteins (ETS2 and FLI1) both in vitro and in vivo. Indirect immunofluorescence demonstrated that EAPII is predominately localized to the nucleus of mammalian cells. EAPII negatively modulates ETS1 transcriptional activity and attenuates synergistic transactivation by ETS1 and AP-1. Significantly, re-expression of EAPII inhibits the migration of epithelial cancer cells, but does not affect cell viability. Therefore, EAPII is a novel ETS1 modulator that regulates specific aspects of the ETS1 functions.
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Acknowledgements
We thank Dr R Brent (The Molecular Sciences Institute, Berkely, CA, USA) for generously providing the yeast two-hybrid reagents, Dr R Tjian (University of California, Berkeley) for the pCMV-c-fos and pCMV-c-jun plasmids, and Drs J Rutter and C Brinckerhoff (Dartmouth Medical School, NH) for the pGL3-MMP1 plasmid. We thank Dr T Hsu for critical review of the manuscript. The GenBank accession number for the sequence of EAPII reported in this paper is AF201687, jointly deposited with Dr Takis S Papas. This study is dedicated to the memory of Dr Takis S Papas, a mentor, scientific colleague and friend. This work was supported in part by American Cancer Society Grant IRG97-151 and Start-up fund from Medical University of South Carolina (RL) and a National Institutes of Health Grant P01CA78582 (DKW).
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Pei, H., Yordy, J., Leng, Q. et al. EAPII interacts with ETS1 and modulates its transcriptional function. Oncogene 22, 2699–2709 (2003). https://doi.org/10.1038/sj.onc.1206374
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DOI: https://doi.org/10.1038/sj.onc.1206374
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