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  • Oncogenomics
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The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies

Oncogene volume 21, pages 6703–6712 (2002)Cite this article

Abstract

The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped to the MTG16a N-terminal region. MTG16a, like MTG8, the nuclear corepressor deranged by the t (8; 21), is capable to interact with specific histone deacetylases (HDACs) suggesting that the protein may mediate silencing of nucleolar gene transcription. In addition, MTG16a is capable to form oligomers with other MTG proteins. As a consequence of the t (16; 21) the AML1 DNA-binding domain replaces the MTG16a N-terminal region. The AML1-MTG16 fusion protein is targeted to the nucleoplasm where it is capable to oligomerize with MTG16a and interact with HDAC1 and HDAC3. The deficiency of HDAC-containing complexes at nucleolar sites and the accumulation of HDAC-containing complexes at AML1-sites may be critical in the pathogenesis of t (16; 21) myeloid malignancies.

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Acknowledgements

We are grateful to Dr Enzo Zimarino, DIBIT, Milan, Italy for his help with the inter-species hybrid assay. This work has been partially funded by an AIRC (Italy) award to N Sacchi. S Rossetti is sponsored by a Foreign Exchange Fellowship, University of Milan.

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Authors and Affiliations

  1. Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands

    André T Hoogeveen, Stefano Rossetti, Violeta Stoyanova, Joris Schonkeren & Leontine van Unen

  2. Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy

    Angelia Fenaroli & Luisa Schiaffonati

  3. San Paolo University Hospital, University of Milan, Milan, Italy

    Nicoletta Sacchi

  4. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA

    Nicoletta Sacchi

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  1. André T Hoogeveen
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Hoogeveen, A., Rossetti, S., Stoyanova, V. et al. The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies. Oncogene 21, 6703–6712 (2002). https://doi.org/10.1038/sj.onc.1205882

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