Increased O-GlcNAcylation of c-Myc promotes Pre-B cell proliferation

Cited 9 time in scopus
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Title
Increased O-GlcNAcylation of c-Myc promotes Pre-B cell proliferation
Author(s)
Da Hee Lee; Na Eun Kwon; W J Lee; Moo-Seung LeeDoo-Jin KimJi Hyung KimSung-Kyun Park
Bibliographic Citation
Cells, vol. 9, pp. 158-158
Publication Year
2020
Abstract
O-linked β-N-acetylglucosamine (O-GlcNAc) modification regulates the activity of hundreds of nucleocytoplasmic proteins involved in a wide variety of cellular processes, such as gene expression, signaling, and cell growth; however, the mechanism underlying the regulation of B cell development and function by O-GlcNAcylation remains largely unknown. Here, we demonstrate that changes in cellular O-GlcNAc levels significantly affected the growth of pre-B cells, which rapidly proliferate to allow expansion of functional clones that express successfully rearranged heavy chains at the pro-B stage during early B cell development. In our study, the overall O-GlcNAc levels in these proliferative pre-B cells, which are linked to the glucose uptake rate, were highly induced when compared with those in pro-B cells. Thus, pharmacologically, genetically, or nutritionally, inhibition of O-GlcNAcylation in pre-B cells markedly downregulated c-Myc expression, resulting in cell cycle arrest via blockade of cyclin expression. Importantly, the population of B cells after the pro-B cell stage in mouse bone marrow was severely impaired by the administration of an O-GlcNAc inhibitor. These results strongly suggest that O-GlcNAcylation-dependent expression of c-Myc represents a new regulatory component of pre-B cell proliferation, as well as a potential therapeutic target for the treatment of pre-B cell-derived leukemia.
Keyword
O-GlcNAcylationc-Mycpre-B cellproliferation
ISSN
2073-4409
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/cells9010158
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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