The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex
- Author(s)
- Dolezal, E; Infantino, S; Drepper, F; Borsig, T; Singh, A; Wossning, T; Fiala, GJ; Minguet, S; Warscheid, B; Tarlinton, DM; Jumaa, H; Medgyesi, D; Reth, M;
- 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
- Research Division(s)
- Immunology
- PubMed ID
- 28628091
- Publisher's Version
- https://doi.org/10.1038/ni.3774
- NHMRC Grants
- NHMRC/1054925,
- Terms of Use/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