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MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins

Author

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  • Yosuke Komata

    (National Cancer Center)

  • Akinori Kanai

    (the University of Tokyo
    Hiroshima University)

  • Takahiro Maeda

    (Kyushu University Graduate School of Medical Sciences)

  • Toshiya Inaba

    (Hiroshima University)

  • Akihiko Yokoyama

    (National Cancer Center)

Abstract

Changes in the transcriptional machinery cause aberrant self-renewal of non-stem hematopoietic progenitors. AF10 fusions, such as CALM-AF10, are generated via chromosomal translocations, causing malignant leukemia. In this study, we demonstrate that AF10 fusion proteins cause aberrant self-renewal via ENL, which binds to MOZ/MORF lysine acetyltransferases (KATs). The interaction of ENL with MOZ, via its YEATS domain, is critical for CALM-AF10-mediated leukemic transformation. The MOZ/ENL complex recruits DOT1L/AF10 fusion complexes and maintains their chromatin retention via KAT activity. Therefore, inhibitors of MOZ/MORF KATs directly suppress the functions of AF10 fusion proteins, thereby exhibiting strong antitumor effects on AF10 translocation-induced leukemia. Combinatorial inhibition of MOZ/MORF and DOT1L cooperatively induces differentiation of CALM-AF10-leukemia cells. These results reveal roles for the MOZ/ENL complex as an essential recruiting factor of the AF10 fusion/DOT1L complex, providing a rationale for using MOZ/MORF KAT inhibitors in AF10 translocation-induced leukemia.

Suggested Citation

  • Yosuke Komata & Akinori Kanai & Takahiro Maeda & Toshiya Inaba & Akihiko Yokoyama, 2023. "MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37712-5
    DOI: 10.1038/s41467-023-37712-5
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    1. Vincenzo Calvanese & Andrew T. Nguyen & Timothy J. Bolan & Anastasia Vavilina & Trent Su & Lydia K. Lee & Yanling Wang & Fides D. Lay & Mattias Magnusson & Gay M. Crooks & Siavash K. Kurdistani & Hann, 2019. "MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment," Nature, Nature, vol. 576(7786), pages 281-286, December.
    2. Michael A. Erb & Thomas G. Scott & Bin E. Li & Huafeng Xie & Joshiawa Paulk & Hyuk-Soo Seo & Amanda Souza & Justin M. Roberts & Shiva Dastjerdi & Dennis L. Buckley & Neville E. Sanjana & Ophir Shalem , 2017. "Transcription control by the ENL YEATS domain in acute leukaemia," Nature, Nature, vol. 543(7644), pages 270-274, March.
    3. Laura MacPherson & Juliana Anokye & Miriam M. Yeung & Enid Y. N. Lam & Yih-Chih Chan & Chen-Fang Weng & Paul Yeh & Kathy Knezevic & Miriam S. Butler & Annabelle Hoegl & Kah-Lok Chan & Marian L. Burr &, 2020. "HBO1 is required for the maintenance of leukaemia stem cells," Nature, Nature, vol. 577(7789), pages 266-270, January.
    4. Jonathan B. Baell & David J. Leaver & Stefan J. Hermans & Gemma L. Kelly & Margs S. Brennan & Natalie L. Downer & Nghi Nguyen & Johannes Wichmann & Helen M. McRae & Yuqing Yang & Ben Cleary & H. Rache, 2018. "Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth," Nature, Nature, vol. 560(7717), pages 253-257, August.
    5. Liling Wan & Hong Wen & Yuanyuan Li & Jie Lyu & Yuanxin Xi & Takayuki Hoshii & Julia K. Joseph & Xiaolu Wang & Yong-Hwee E. Loh & Michael A. Erb & Amanda L. Souza & James E. Bradner & Li Shen & Wei Li, 2017. "ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia," Nature, Nature, vol. 543(7644), pages 265-269, March.
    6. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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