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Cooperative effect of ribosomal protein s19 and Pim-1 kinase on murine c-Myc expression and myeloid/erythroid cellularity

Abstract

Diamond Blackfan anemia (DBA) is a bone marrow failure syndrome associated with heterozygous mutations in the ribosomal protein S19 (RPS19) gene in a subgroup of patients. One of the interacting partners with RPS19 is the oncoprotein PIM-1 kinase. We intercrossed Rps19+/- and Pim-1-/- mice strains to study the effect from the disruption of both genes. The double mutant (Rps19+/-Pim-1-/-) mice display normal growth with increased peripheral white- and red blood cell counts when compared to the w.t. mice (Rps19+/+Pim-1+/+). Molecular analysis of bone marrow cells in Rps19+/-Pim-1-/- mice revealed up-regulated levels of c-Myc and the anti-apoptotic factors Bcl2, BclXL and Mcl-1. This is associated with a reduction of the apoptotic factors Bak and Caspase 3 as well as the cell cycle regulator p21. Our findings suggest that combined Rps19 insufficiency and Pim-1 deficiency promotes murine myeloid cell growth through a deregulation of c-Myc and a simultaneous up-regulation of anti-apoptotic Bcl proteins.

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Correspondence to Niklas Dahl.

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Frojmark, AS., Badhai, J., Klar, J. et al. Cooperative effect of ribosomal protein s19 and Pim-1 kinase on murine c-Myc expression and myeloid/erythroid cellularity. Nat Prec (2009). https://doi.org/10.1038/npre.2009.2882.1

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Keywords

  • apoptotic factors
  • Rps19
  • Pim-1
  • erythropoiesis
  • myelopoiesis
  • c-Myc

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