Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging.
Mo-MLV infection of E mu-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 E mu-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.
van Lohuizen
M
M
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Verbeek
S
S
Scheijen
B
B
Wientjens
E
E
van der Gulden
H
H
Berns
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D063150:Polycomb Repressive Complex 1; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins; D011533:Proviruses / Q000235:genetics; D012097:Repressor Proteins; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D016335:Zinc Fingers / Q000235:genetics
C489421:Bmi1 protein, mouse; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1