Cell
Volume 65, Issue 5, 31 May 1991, Pages 737-752
Journal home page for Cell

Identification of cooperating oncogenes in Eμ-myc transgenic mice by provirus tagging

https://doi.org/10.1016/0092-8674(91)90382-9Get rights and content

Abstract

Mo-MLV infection of Eμ-myc transgenic mice results in a dramatic acceleration of pre-B cell lymphomagenesis. We have used provirus tagging to identify genes that cooperate with the Eμ-myc transgene in B cell transformation. Here we report on the identification of four loci, pim-1, bmi-1, pal-1, and bla-1, which are occupied by proviruses in 35%, 35%, 28%, and 14% of the tumors, respectively. bmi-1, pal-1, and bla-1 represent novel common proviral insertion sites. The bmi-1 gene encodes a 324 amino acid protein with a predominantly nuclear localization. bmi-1 is highly conserved in evolution and contains several motifs frequently found in transcriptional regulators, including a new putative zinc finger motif. No genes have yet been assigned to pal-1 and bla-1. The distribution of proviruses over the four common insertion sites suggests that provirus tagging can be used not only to identify the cooperating oncogenes but also to assign these genes to distinct complementation groups in tumorigenesis.

References (79)

  • KadonagaJ.T. et al.

    Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain

    Cell

    (1987)
  • KalderonD. et al.

    A short amino acid sequence able to specify nuclear location

    Cell

    (1984)
  • KleinG.

    Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men

    Cell

    (1983)
  • KlemszM.J. et al.

    The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene

    Cell

    (1990)
  • KozakM.

    Bifunctional messenger RNAs in eukaryotes

    Cell

    (1986)
  • KozakM.

    At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells

    J. Mol. Biol.

    (1987)
  • LanfordR.E. et al.

    Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen

    Cell

    (1984)
  • LangdonW.Y. et al.

    The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice

    Cell

    (1986)
  • McGinnisW. et al.

    Molecular cloning and chromosome mapping of a mouse DNA sequence homologous to homeotic genes of Drosophila

    Cell

    (1984)
  • MeltonD.W. et al.

    Expression of the mouse HPRT gene: deletional analysis of the promoter region of an X-chromosome linked housekeeping gene

    Cell

    (1986)
  • MiyamotoM. et al.

    Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements

    Cell

    (1988)
  • RichardsonW.D. et al.

    Nuclear location signals in polyoma virus large-T

    Cell

    (1986)
  • SchatzD.G. et al.

    The V(D)J recombination activating gene, RAG-1

    Cell

    (1989)
  • ScottM.P. et al.

    The structure and function of the homeodomain

    Biochim. Biophys. Acts

    (1989)
  • SeltenG. et al.

    The primary structure of the putative oncogenepim-1 shows extensive homology with protein kinases

    Cell

    (1986)
  • van LohuizenM. et al.

    Predisposition to lymphoma genesis inpim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors

    Cell

    (1989)
  • AdamsJ.M. et al.

    The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice

    Nature

    (1985)
  • BergJ.M.

    Metal ions in proteins: structural and functional roles

  • BlackwellT.K. et al.

    Sequence-specific DNA binding by the c-myc protein

    Science

    (1990)
  • BreuerM.L. et al.

    Evidence for the involvement ofpim-2, a new common proviral insertion site, in progression of lymphomas

    EMBO J.

    (1989)
  • BuchbergA.M. et al.

    Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice

    Oncogene Res.

    (1988)
  • ChanelR. et al.

    Potential DNA-binding domains in the RAD18 gene product ofSaccharomyces cerevisiae

    Gene

    (1988)
  • ChouP.Y. et al.

    Empirical predictions of protein conformation

    Annu. Rev. Biochem.

    (1978)
  • ColeM.D.

    Themyc oncogene: its role in transformation and differentiation

    Annu. Rev. Genet.

    (1986)
  • CollumR.G. et al.

    Aremyc proteins transcription factors?

    Cancer Cells

    (1990)
  • CopelandN.G. et al.

    Development and applications of a molecular genetic linkage map of the mouse genome

    Trends Genet.

    (1991)
  • CoppolaJ.A. et al.

    Constitutive c-myc oncogene expression blocks mouse erythroleukaemia cell differentiation but not commitment

    Nature

    (1986)
  • CoryS. et al.

    Transgenic mice and oncogenesis

    Annu. Rev. Immunol.

    (1988)
  • CuypersH.T. et al.

    Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region

    Cell

    (1984)
  • Cited by (711)

    • BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm

      2021, Biochemical and Biophysical Research Communications
    View all citing articles on Scopus
    *

    Present address: Department of Experimental Immunology, AZU, University of Utrecht, 3508 GA Utrecht, The Netherlands.

    View full text