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ETO-2, a new member of the ETO-family of nuclear proteins

Abstract

The t(8;21) is associated with 12 – 15% of acute myelogenous leukemias of the M2 subtype. The translocation results in the fusion of two genes, AML1 (CBFA2) on chromosome 21 and ETO (MTG8) on chromosome 8. AML1 encodes a DNA binding factor; the ETO protein product is less well characterized, but is thought to be a transcription factor. Here we describe the isolation and characterization of ETO-2, a murine cDNA that encodes a new member of the ETO family of proteins. ETO-2 is 75% identical to murine ETO and shares very high sequence identities over four regions of the protein with ETO (domain I – III and zinc-finger). Northern analysis identifies ETO-2 transcripts in many of the murine tissues analysed and in the developing mouse embryo. ETO-2 is also expressed in myeloid and erythroid cell lines. We confirmed the nuclear localization of ETO-2 and demonstrated that domain III and the zinc-finger region are not required for nuclear localization. We further showed that a region within ETO, containing domain II, mediates dimerization among family members. This region is conserved in the oncoprotein AML-1/ETO. The recent identification of another ETO-like protein, myeloid translocation gene-related protein 1, together with the data presented here, demonstrates that at least three ETO proteins exist with the potential to form dimers in the cell nucleus.

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Acknowledgements

The authors would like to thank Dr Kelly Tatchell for the gift of the monoclonal antibody 9E10 and Dr Paul Erickson for the gift of the murine ETO cDNA. We are grateful to Dr Scott Hiebert and Dr Sue Watson for critical reading of the manuscript and to John Riley for expert assistance. SM and JND would especially like to thank Ellie Shaina Davis. This work was supported in part by a grant to SM from the National Institutes of Health (R29-CA76186) and by money provided by the Departments of Biochemistry (SM and JND) and Urology, (BJW) LSUMC-S, the Feist-Weiller Cancer Center, LSUMC-S and the Virginia K Shehee Biomedical Research Foundation of Northwest Louisiana (SM and JND).

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Davis, J., Williams, B., Herron, J. et al. ETO-2, a new member of the ETO-family of nuclear proteins. Oncogene 18, 1375–1383 (1999). https://doi.org/10.1038/sj.onc.1202412

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