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  • The EMBO Journal (2009) 28, 1392 - 1406
  • doi:10.1038/emboj.2009.100

Published online: 16 April 2009

MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells

Jessica Schwermann1,4, Chozhavendan Rathinam2,4,a, Maria Schubert1,4, Stefanie Schumacher1, Fatih Noyan2, Haruhiko Koseki3, Alexey Kotlyarov1,4, Christoph Klein2,4 and Matthias Gaestel1,4

  1. Institute of Biochemistry, Hannover Medical School, Hannover, Germany
  2. Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany
  3. RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Japan
  4. These authors contributed equally to this work

Correspondence to:

Matthias Gaestel, Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. Tel.: +49 511 532 2825; Fax: +49 511 532 2827; E-mail: gaestel.matthias@mh-hannover.de

aPresent address: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA

Received 10 October 2008; Accepted 24 March 2009

The structurally related MAPK-activated protein kinases (MAPKAPKs or MKs) MK2, MK3 and MK5 are involved in multiple cellular functions, including cell-cycle control and cellular differentiation. Here, we show that after deregulation of cell-cycle progression, haematopoietic stem cells (HSCs) in MK2-deficient mice are reduced in number and show an impaired ability for competitive repopulation in vivo. To understand the underlying molecular mechanism, we dissected the role of MK2 in association with the polycomb group complex (PcG) and generated a MK2 mutant, which is no longer able to bind to PcG. The reduced ability for repopulation is rescued by re-introduction of MK2, but not by the Edr2-non-binding mutant of MK2. Thus, MK2 emerges as a regulator of HSC homeostasis, which could act through chromatin remodelling by the PcG complex.

  • Keywords:

    • chromatin remodelling,
    • haematopoiesis,
    • mouse knockout,
    • protein kinase
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