Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Dolezal, Elmar1, 2, 3
  • Infantino, Simona4, 5, 6
  • Drepper, Friedel7, 8
  • Börsig, Theresa1
  • Singh, Aparajita1, 2
  • Wossning, Thomas2
  • Fiala, Gina J1, 7, 9
  • Minguet, Susana1, 7, 9
  • Warscheid, Bettina7, 8
  • Tarlinton, David M4, 5, 6
  • Jumaa, Hassan1, 7, 10
  • Medgyesi, David1, 2, 7
  • Reth, Michael1, 2, 7
  • 1 Department for Molecular Immunology, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany. , (Germany)
  • 2 Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. , (Germany)
  • 3 Spemann Graduate School of Biology and Medicine (SGBM) Albert-Ludwigs University of Freiburg, Freiburg, Germany. , (Germany)
  • 4 Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. , (Australia)
  • 5 Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. , (Australia)
  • 6 Department of Immunology and Pathology, Monash University, Melbourne, Australia. , (Australia)
  • 7 BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs University of Freiburg, Freiburg, Germany. , (Germany)
  • 8 Department of Biochemistry and Functional Proteomics, Faculty of Biology, Albert-Ludwigs University of Freiburg, Freiburg, Germany. , (Germany)
  • 9 Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, Freiburg, Germany. , (Germany)
  • 10 Institute of Immunology, University Hospital Ulm, Ulm, Germany. , (Germany)
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Aug 01, 2017
Volume
18
Issue
8
Pages
911–920
Identifiers
DOI: 10.1038/ni.3774
PMID: 28628091
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times