The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex
Journal Title
Nat Immunol
Publication Type
Journal Article in press
Abstract
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression. Moreover, BTG2 in concert with PRMT1 efficiently blocked the proliferation of BCR-ABL1-transformed pre-B cells in vitro and in vivo. Our results identify a key molecular mechanism by which the BTG2-PRMT1 module regulates pre-B cell differentiation and inhibits pre-B cell leukemogenesis.
Publisher
Springer Nature
WEHI Research Division(s)
Immunology
PubMed ID
28628091
Publisher's Version
https://doi.org/10.1038/ni.3774
NHMRC Grants
NHMRC/1054925
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-06-26 02:15:24
Last Modified: 2017-06-26 02:34:29
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