flvi-2, a target of retroviral insertional mutagenesis in feline thymic lymphosarcomas, encodes bmi-1.
LC-FeLV is a myc-containing strain of feline leukemia virus which induces thymic lymphosarcoma in the domestic cat with short latency. A locus in feline DNA, termed flvi-2, is commonly interrupted in naturally occurring and experimentally induced thymic lymphosarcomas containing LC-FeLV; thus, interruption of a gene encoded by flvi-2 may cooperate with the myc oncogene in the induction of T-cell tumors by LC-FeLV. Clones homologous to flvi-2 have been isolated from a normal human thymus cDNA library. Nucleotide sequence analysis of the cDNA clones demonstrates that flvi-2 encodes bmi-1, a gene previously identified as a target for MoMuLV integration and as a myc-collaborator in retrovirally-induced B-cell lymphomas in E mu-myc transgenic mice. In feline thymic lymphomas, retroviral integrations occur downstream of the gene, and result in enhanced expression of a bmi-1 transcript of normal size. These findings demonstrate the interruption of bmi-1 in natural as well as experimentally induced tumors, implicate the activation of bmi-1 in the induction of T-cell as well as B-cell lymphoma, and support the premise that bmi-1 functions as a myc collaborator.
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
L S
LS
Levy
P A
PA
Lobelle-Rich
J
J
Overbaugh
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats / Q000235:genetics*; D006801:Humans; D005256:Leukemia Virus, Feline / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000382:microbiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D013953:Thymus Neoplasms / Q000235:genetics* / Q000382:microbiology; D016662:Virus Integration; D016335:Zinc Fingers / Q000235:genetics*
C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1