The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex

Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J. Fiala, Susana Minguet, Bettina Warscheid, David M. Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth

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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.

Original languageEnglish
Pages (from-to)911-920
Number of pages10
JournalNature Immunology
Volume18
Issue number8
DOIs
Publication statusPublished - 19 Jul 2017

Cite this

Dolezal, E., Infantino, S., Drepper, F., Börsig, T., Singh, A., Wossning, T., Fiala, G. J., Minguet, S., Warscheid, B., Tarlinton, D. M., Jumaa, H., Medgyesi, D., & Reth, M. (2017). The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. Nature Immunology, 18(8), 911-920. https://doi.org/10.1038/ni.3774