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Loss of MYSM1 inhibits the oncogenic activity of cMYC in B cell lymphoma |
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| Authors: | Yun Hsiao Lin HanChen Wang Amanda Fiore Michael Förster Lin Tze Tung Jad I Belle Francis Robert Jerry Pelletier David Langlais Anastasia Nijnik |
| Affiliation: | 1. Department of Physiology, McGill University, Montreal, QC, Canada;2. Department of Physiology, McGill University, Montreal, QC, Canada McGill University Research Centre on Complex Traits, McGill University, QC, Canada Department of Human Genetics, McGill University, Montreal, QC, Canada Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Software (lead), Writing - review & editing (supporting);3. Department of Physiology, McGill University, Montreal, QC, Canada McGill University Research Centre on Complex Traits, McGill University, QC, Canada Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting);4. Department of Physiology, McGill University, Montreal, QC, Canada McGill University Research Centre on Complex Traits, McGill University, QC, Canada Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Supervision (supporting), Writing - review & editing (supporting);5. Department of Physiology, McGill University, Montreal, QC, Canada McGill University Research Centre on Complex Traits, McGill University, QC, Canada Contribution: Investigation (supporting), Writing - review & editing (supporting);6. Department of Physiology, McGill University, Montreal, QC, Canada McGill University Research Centre on Complex Traits, McGill University, QC, Canada Contribution: Conceptualization (supporting), Supervision (supporting), Writing - review & editing (supporting);7. Department of Biochemistry, McGill University, Montreal, QC, Canada The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada Contribution: Methodology (supporting), Resources (supporting), Supervision (supporting), Writing - review & editing (supporting);8. Department of Biochemistry, McGill University, Montreal, QC, Canada The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada Contribution: Methodology (supporting), Resources (supporting), Supervision (supporting);9. McGill University Research Centre on Complex Traits, McGill University, QC, Canada |
| Abstract: | MYSM1 is a chromatin-binding protein, widely investigated for its functions in haematopoiesis in human and mouse; however, its role in haematologic malignancies remains unexplored. Here, we investigate the cross-talk between MYSM1 and oncogenic cMYC in the transcriptional regulation of genes encoding ribosomal proteins, and the implications of these mechanisms for cMYC-driven carcinogenesis. We demonstrate that in cMYC-driven B cell lymphoma in mouse models, MYSM1-loss represses ribosomal protein gene expression and protein synthesis. Importantly, the loss of MYSM1 also strongly inhibits cMYC oncogenic activity and protects against B cell lymphoma onset and progression in the mouse models. This advances the understanding of the molecular and transcriptional mechanisms of lymphomagenesis, and suggests MYSM1 as a possible drug target for cMYC-driven malignancies. |
| Keywords: | B cell lymphoma chromatin cMYC mouse models transcriptional regulation |