Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice.
To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in E mu-myc transgenic mice. Moloney murine leukemia virus accelerated development of B lymphoid tumors. Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi-1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels. Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene. Thus, myc-induced lymphomagenesis can entail the concerted action of several genes, including the presumptive nuclear regulator bmi-1.
Haupt
Y
Y
Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
Alexander
W S
WS
Barri
G
G
Klinken
S P
SP
Adams
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005803:Genes, Immunoglobulin; D005809:Genes, Regulator; D016259:Genes, myc; D007148:Immunoglobulin mu-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*; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D011506:Proteins; 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; D004268:DNA-Binding Proteins; C498959:Emi1 protein, mouse; D007148:Immunoglobulin mu-Chains; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1