Open AccessLoss of MYSM1 inhibits the oncogenic activity of cMYC in B cell lymphoma
Author(s) -
Lin Yun Hsiao,
Wang HanChen,
Fiore Amanda,
Förster Michael,
Tung Lin Tze,
Belle Jad I,
Robert Francis,
Pelletier Jerry,
Langlais David,
Nijnik Anastasia
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16554
Subject(s) - biology , ribosomal protein , carcinogenesis , lymphoma , cancer research , haematopoiesis , gene , chromatin , b cell lymphoma , b cell , microbiology and biotechnology , genetics , immunology , antibody , stem cell , rna , ribosome
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.