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Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Eμ-myc transgenic mice

1991; Cell Press; Volume: 65; Issue: 5 Linguagem: Inglês

10.1016/0092-8674(91)90383-a

1097-4172

Ygal Haupt, Warren S. Alexander, Gina Barri, S. Peter Klinken, Jerry M. Adams,

RNA Interference and Gene Delivery

To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in Eμ-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.