Pathogenesis of Friend leukemia virus.
Friend leukemia virus complex (FLV) consists of replication-defective, Friend spleen focus-forming virus (F-SFFV) and replication-competent, Friend murine leukemia virus (F-MuLV). We produced transgenic mice possessing F-SFFV gp55 gene and clarified that the gp55 glycoprotein encoded by F-SFFV env-related gene is, by itself, responsible for the initiation of erythroleukemia. The occurrence of erythroleukemia, however, is sporadic in these mice. Erythroleukemia cell lines established from these mice possessed mutations in the p53 allele. One had a temperature-sensitive mutant p53 allele, p53Val-135 and showed induction of apoptosis by expressing a wild-type p53 protein at 32 degrees C. Superinfection of the mice with Moloney murine leukemia virus (Mo-MuLV) conferred 100% induction of erythroleukemia, mutating p53 gene or activating Spfi-1 gene by insertional events. Activation of the JAK/STAT pathway, which is involved in cytokine signaling, was investigated in the gp55 signaling mediated by the erythropoietin receptor. JAK1 and STAT5 were constitutively tyrosine-phosphorylated but the DNA binding activity of STAT5 was not induced.
Ikawa
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Y
Department of Retroviral Regulation, Tokyo Medical and Dental University Medical Research Division, Japan.
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D005091:Exons; D005622:Friend murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D015752:Genes, env; D053613:Janus Kinase 1; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000503:physiopathology* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins; D008979:Moloney murine leukemia virus / Q000472:pathogenicity; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000502:physiology; D012192:Retroviridae Infections / Q000235:genetics / Q000503:physiopathology*; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013155:Spleen Focus-Forming Viruses / Q000235:genetics / Q000472:pathogenicity*; D015534:Trans-Activators / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics / Q000503:physiopathology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D017467:Receptors, Erythropoietin; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1