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The ENL moiety of the childhood leukemia-associated MLL–ENL oncoprotein recruits human Polycomb 3

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Abstract

The translocation t(11;19) is frequently found in acute leukemia in infants. This event truncates the proto-oncogene MLL and fuses the 5′ end of MLL in frame with the ENL gene. ENL contributes a crucial protein–protein interaction domain to the resulting oncoprotein MLL–ENL. Here we show by yeast two-hybrid assays, GST-pull-down experiments and in a far western blot analysis that this domain is necessary and sufficient to recruit a novel member of the human Polycomb protein family (hPc3). hPc3 RNA was detected throughout the human hematopoietic system. Similar to other Polycomb proteins hPc3 acts as a transcriptional repressor. The ENL-hPc3 interaction was verified by mutual co-precipitation of the proteins from cell extracts. ENL and hPc3 tagged with fluorescent proteins co-localized in living cells in a nuclear dot pattern. An internal region of hPc3 was responsible for binding to ENL. Finally, hPc3 binds to the C-terminus of AF9, another common MLL fusion partner. The recruitment of a repressive function by ENL opens up a new insight into a possible mechanism of leukemogenesis by the fusion protein MLL–ENL.

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Acknowledgements

The authors wish to thank Marion Hamacher and Etelka Elekes for technical assistance and Georg Fey for continous support. This work was supported by grant SFB466/C7 and partially by grants SFB473/B10 and SL27/4-1 from the DFG. RK Slany is a recipient of a Ria Freifrau-von-Fritsch Stiftung career development award.

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Authors and Affiliations

  1. Department of Genetics, University of Erlangen, Staudtstrasse 5, Erlangen, 91058, Germany

    M P García-Cuéllar, O Zilles, S A Schreiner, M Birke & R K Slany

  2. Division of Molecular Immunology, Department of Internal Medicine III, University of Erlangen, Glückstrasse 4, Erlangen, 91056, Germany

    T H Winkler

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  1. M P García-Cuéllar
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  2. O Zilles
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García-Cuéllar, M., Zilles, O., Schreiner, S. et al. The ENL moiety of the childhood leukemia-associated MLL–ENL oncoprotein recruits human Polycomb 3. Oncogene 20, 411–419 (2001). https://doi.org/10.1038/sj.onc.1204108

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  • DOI: https://doi.org/10.1038/sj.onc.1204108

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