Pim-1 kinase phosphorylates RUNX family transcription factors and enhances their activity
1 Turku Centre for Biotechnology, University of Turku/Åbo Akademi University, Tykistökatu 6 B, 20520 Turku, Finland
2 Turku Graduate School of Biomedical Sciences, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland
3 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore
BMC Cell Biology 2006, 7:21 doi:10.1186/1471-2121-7-21Published: 9 May 2006
The pim family genes encode oncogenic serine/threonine kinases which in hematopoietic cells have been implicated in cytokine-dependent signaling as well as in lymphomagenesis, especially in cooperation with other oncogenes such as myc, bcl-2 or Runx family genes. The Runx genes encode α-subunits of heterodimeric transcription factors which regulate cell proliferation and differentiation in various tissues during development and which can become leukemogenic upon aberrant expression.
Here we have identified novel protein-protein interactions between the Pim-1 kinase and the RUNX family transcription factors. Using the yeast two-hybrid system, we were able to show that the C-terminal part of human RUNX3 associates with Pim-1. This result was confirmed in cell culture, where full-length murine Runx1 and Runx3 both coprecipitated and colocalized with Pim-1. Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.
Altogether, our results suggest that mammalian RUNX family transcription factors are novel binding partners and substrates for the Pim-1 kinase, which may be able to regulate their activities during normal hematopoiesis as well as in leukemogenesis.