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CBFβ-SMMHC regulates ribosomal gene transcription and alters ribosome biogenesis

Leukemia volume 31, pages 1443–1446 (2017)Cite this article

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The core-binding factor (CBF) complex is a heterodimeric transcription factor comprising a CBFβ subunit and a variable DNA-binding RUNX subunit, usually RUNX1 in hematopoietic cells. Aside from its critical hematopoietic functions, CBF regulates the expression of ribosomal protein genes and ribosomal RNA (rRNA) in a cell context-dependent manner.1, 2, 3 Intriguingly, this function may have implications for the pathogenesis of acute myeloid leukemia (AML), as reduced ribosome biogenesis in RUNX1-deficient hematopoietic stem cells has recently been proposed to confer a survival advantage that favors outgrowth of preleukemic RUNX1-deficient clones.3 Furthermore, AML-associated fusion proteins that arise from translocations of CBF subunit genes have been shown to occupy nucleolar organizing regions at mitotic chromosomes,4, 5 suggesting that ribosomal homeostasis might be altered in CBF-AML.

The AML-associated CBFβ-MYH11 translocation arises from either an inv(16)(p13;q22) or t(16;16)(p13;q22) and generates the CBFβ-SMMHC fusion protein. The oncoprotein has been thought to subvert wild-type CBF function primarily through cytoplasmic sequestration of RUNX1 and by the recruitment of transcriptional corepressors, which inhibit the expression of CBF-regulated genes.6, 7 It is, however, likely that CBFβ-SMMHC has additional activities that contribute to AML oncogenesis. For example, we have shown that a significant proportion of cellular CBFβ-SMMHC is present in the nucleus, binds to chromatin and preferentially co-localizes with RUNX1 at the promoters of transcribed loci, suggesting that CBFβ-SMMHC may also participate in the activation of RUNX1 target genes.8

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Acknowledgements

JB was supported by a Kay Kendall Leukaemia Fund Intermediate Research Fellowship. The Necker laboratory is supported by the Association Laurette Fugain, La Ligue Contre le Cancer and the INCa CARAMELE Translational Research and PhD programs. The Fumagalli laboratory is supported by grants from the Agence Nationale de la Recherche and from the Fondation ARC Pour la Recherche sur le Cancer. The Martens laboratory was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282510-BLUEPRINT and the Dutch Cancer Foundation (KUN 2011-4937).

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Author notes

  1. A Mandoli and A Radhouane: These authors contributed equally to this work.

Authors and Affiliations

  1. Université Paris Descartes Sorbonne Cité, Institut Necker Enfants Malades (INEM), Institut National de la Santé et de la Recherche Médicale (INSERM) U1151, Paris, France

    G Cordonnier, A Radhouane, G Hypolite, L Lhermitte, V Asnafi, E Macintyre, S Fumagalli & J Bond

  2. Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants Malades, Paris, France

    G Cordonnier, G Hypolite, L Lhermitte, V Asnafi, E Macintyre & J Bond

  3. Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands

    A Mandoli & J H A Martens

  4. Technological Advances for Genomics and Clinics (TAGC), INSERM U1090, Aix-Marseille University UMR-S 1090, Marseille, France

    M Belhocine

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  1. G Cordonnier
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Correspondence to S Fumagalli or J Bond.

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Cordonnier, G., Mandoli, A., Radhouane, A. et al. CBFβ-SMMHC regulates ribosomal gene transcription and alters ribosome biogenesis. Leukemia 31, 1443–1446 (2017). https://doi.org/10.1038/leu.2017.53

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