Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2

EMBO J. 1995 Jun 1;14(11):2536-44.


The Pim-1 proto-oncogene is one of the most potent collaborators of the myc proto-oncogenes in inducing lymphomagenesis in mice. Contrary to the profound effects when overexpressed in vivo, Pim-1-deficient mice showed only subtle phenotypic alterations, which could indicate the presence of redundantly acting genes. In line with this, a PCR-based screen has led to the identification of a closely homologous gene, Pim-2. The X-linked Pim-2 gene is 53% identical to Pim-1 at the amino acid level and shares substrate preference and the usage of non-AUG initiation codons with Pim-1. We have used these data to test whether the strong synergistic interaction between Pim-1 and c-myc can be utilized to gain access to Pim-1 compensatory pathways. We reasoned that, upon proviral tagging in compound mutant mice (E mu-myc/Pim-1-/- mice), the selective advantage of cells carrying provirally activated genes, that act downstream from or parallel to Pim-1, would increase. We show here that this is the case. A dramatic increase (from 15 to 80%) was found in the frequency of proviral activation of the Pim-2 gene. These data show that the described strategy of 'complementation tagging' represents a powerful new tool to identify components of pathways involved in processes as complex as multistep tumorigenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Female
  • Gene Expression Regulation
  • Genes, myc*
  • Lymphoma / etiology
  • Lymphoma / genetics
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-pim-1
  • Proto-Oncogenes*
  • Proviruses / genetics*
  • Sequence Homology, Amino Acid


  • DNA, Complementary
  • Pim2 protein, mouse
  • Proto-Oncogene Proteins
  • Pim1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1

Associated data

  • GENBANK/L41495
  • GENBANK/L41496