C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein

Blood. 2011 Oct 27;118(17):4682-9. doi: 10.1182/blood-2011-05-354076. Epub 2011 Sep 7.


The three-amino-acid loop extension (TALE) class homeodomain proteins MEIS1 and PKNOX1 (PREP1) share the ability to interact with PBX and HOX family members and bind similar DNA sequences but appear to play opposing roles in tumor development. Elevated levels of MEIS1 accelerate development of HOX- and MLL-induced leukemias, and this pro-tumorigenic property has been associated with transcriptional activity of MEIS1. In contrast, reduction of PKNOX1 levels has been linked with cancer development despite the absence of an identifiable transactivating domain. In this report, we show that a chimeric protein generated by fusion of the MEIS1 C-terminal region encompassing the transactivating domain with the full-length PKNOX1 (PKNOX1-MC) acquired the ability to accelerate the onset of Hoxa9-induced leukemia in the mouse bone marrow transduction/transplantation model. Gene expression profiling of primary bone marrow cells transduced with Hoxa9 plus Meis1, or Hoxa9 plus Pknox1-MC revealed perturbations in overlapping functional gene subsets implicated in DNA packaging, chromosome organization, and in cell cycle regulation. Together, results presented in this report suggest that the C-terminal domain of MEIS1 confers to PKNOX1 an ectopic transactivating function that promotes leukemogenesis by regulating expression of genes involved in chromatin accessibility and cell cycle progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cells, Cultured
  • Chromatin / metabolism
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Leukemia / genetics
  • Leukemia / metabolism
  • Leukemia / mortality
  • Leukemia / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins / metabolism
  • Oncogene Proteins / physiology
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Interaction Domains and Motifs / genetics
  • Protein Interaction Domains and Motifs / physiology*
  • Transfection


  • Chromatin
  • Homeodomain Proteins
  • Meis1 protein, mouse
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Oncogene Proteins
  • Pknox1 protein, mouse
  • homeobox protein HOXA9