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.
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%0 Journal Article
%1 dolezalBTG2PRMT1ModuleLimits2017
%A Dolezal, Elmar
%A Infantino, Simona
%A Drepper, Friedel
%A Börsig, Theresa
%A Singh, Aparajita
%A Wossning, Thomas
%A Fiala, Gina J.
%A Minguet, Susana
%A Warscheid, Bettina
%A Tarlinton, David M.
%A Jumaa, Hassan
%A Medgyesi, David
%A Reth, Michael
%C United States
%D 2017
%J Nature immunology
%K 4/*metabolism,DNA-Binding Animals,Cell B-Lymphocyte/genetics,Genes B-Lymphoid/cytology/*metabolism,Protein-Arginine Cells Chain Chains/genetics,Lymphopoiesis/*genetics,Mass Checkpoints,Cell Cycle Cytometry,Gene D3/*metabolism,Cyclin-Dependent Differentiation/genetics,Cell Interfering,to_read,Tumor Kinase Knockdown Light N-Methyltransferases/*genetics/metabolism,Real-Time Polymerase Proliferation/*genetics,Cyclin Proteins/*genetics/metabolism Proteins/*genetics/metabolism,Immunoglobulin Proteins/genetics/metabolism,Flow Proteins/genetics/metabolism,Immediate-Early Reaction,RNA Rearrangement Small Spectrometry,Mice,Precursor Suppressor Techniques,Gene abl/genetics,Homeodomain
%N 8
%P 911--920
%R 10.1038/ni.3774
%T The BTG2-PRMT1 Module Limits Pre-B Cell Expansion by Regulating the CDK4-Cyclin-D3 Complex.
%V 18
%X 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.
@article{dolezalBTG2PRMT1ModuleLimits2017,
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.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {United States},
author = {Dolezal, Elmar and Infantino, Simona and Drepper, Friedel and B{\"o}rsig, Theresa and Singh, Aparajita and Wossning, Thomas and Fiala, Gina J. and Minguet, Susana and Warscheid, Bettina and Tarlinton, David M. and Jumaa, Hassan and Medgyesi, David and Reth, Michael},
biburl = {https://www.bibsonomy.org/bibtex/28d4fd7734586ae51d9035826855d5c43/warscheidlab},
doi = {10.1038/ni.3774},
interhash = {23434109b8e78b4af71a11d970a33f55},
intrahash = {8d4fd7734586ae51d9035826855d5c43},
issn = {1529-2916 1529-2908},
journal = {Nature immunology},
keywords = {4/*metabolism,DNA-Binding Animals,Cell B-Lymphocyte/genetics,Genes B-Lymphoid/cytology/*metabolism,Protein-Arginine Cells Chain Chains/genetics,Lymphopoiesis/*genetics,Mass Checkpoints,Cell Cycle Cytometry,Gene D3/*metabolism,Cyclin-Dependent Differentiation/genetics,Cell Interfering,to_read,Tumor Kinase Knockdown Light N-Methyltransferases/*genetics/metabolism,Real-Time Polymerase Proliferation/*genetics,Cyclin Proteins/*genetics/metabolism Proteins/*genetics/metabolism,Immunoglobulin Proteins/genetics/metabolism,Flow Proteins/genetics/metabolism,Immediate-Early Reaction,RNA Rearrangement Small Spectrometry,Mice,Precursor Suppressor Techniques,Gene abl/genetics,Homeodomain},
langid = {english},
month = aug,
number = 8,
pages = {911--920},
pmid = {28628091},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {The {{BTG2-PRMT1}} Module Limits Pre-{{B}} Cell Expansion by Regulating the {{CDK4-Cyclin-D3}} Complex.},
volume = 18,
year = 2017
}