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Loss of MYSM1 inhibits the oncogenic activity of cMYC in B cell lymphoma.

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.

SUBMITTER: Lin YH

PROVIDER: S-EPMC8278115 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Loss of MYSM1 inhibits the oncogenic activity of cMYC in B cell lymphoma.

Lin Yun Hsiao YH Wang HanChen H Fiore Amanda A Förster Michael M Tung Lin Tze LT Belle Jad I JI Robert Francis F Pelletier Jerry J Langlais David D Nijnik Anastasia A

Journal of cellular and molecular medicine 20210611 14

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 protei ...[more]

PMID: 34114734

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