Oncogene cooperativity in Friend erythroleukemia: erythropoietin receptor activation by the env gene of SFFV leads to transcriptional upregulation of PU.1, independent of SFFV proviral insertion

Subtle distinct regulations of late erythroid molecular events by PI3K/AKT-mediated activation of Spi-1/PU.1 oncogene autoregulation loop

“…Inihibition of PI3K/AKT blocks PI3K/AKT-mediated phosphorylation of Spi-1/PU.1 and subsequently inactivates Spi-1/PU.1-mediated autoregulation. Supportive of this model is the observation that Epo-R activation of SFFV by the env gene leads to transcriptional upregulation of Spi-1/PU.1 in the absence of Epo and in the absence of an integrated SFFV provirus within the Spi-1/PU.1 locus (Afrikanova et al, 2002).…”

“…Hereafter, cell clones with integrated SFFV provirus in the spi-1/pu.1 gene locus expand and display high level of Spi-1/PU.1, involving the activation of spi-1/pu.1 gene transcription by an enhancer element present in the SFFV long terminal repeat (Moreau-Gachelin et al, 1989;Okuno et al, 2005). High levels of Spi-1/PU.1 protein are necessary to maintain the transformed phenotype (Afrikanova et al, 2002).…”

Functional Cross-Antagonism between Transcription Factors FLI-1 and EKLF

“…Importantly, this transforming property of SPI-1/PU.1 evidenced in avian erythroblasts is strictly dependent upon specifically activated forms of EPO-R (52). Cooperation between SPI-1/PU.1 and EPO-R activation by the gp55 env protein encoded by SFFV has also been recently demonstrated with mice (1). One of the known contributions of SPI-1/PU.1 in erythroleukemia is to inhibit the activity of GATA-1, which is one of the most critical DNA binding factors required for erythroid cell differentiation and survival.…”

Resistance to Friend Virus-Induced Erythroleukemia in W / W v Mice Is Caused by a Spleen-Specific Defect Which Results in a Severe Reduction in Target Cells and a Lack of Sf-Stk Expression

“…These studies showed that Spi-1 expression was required for the Kit/SCF-dependent increase in proliferation, but this conclusion is complicated by the observation that overexpression of Spi-1 due to proviral insertion is a relatively late event in the pathogenesis of Friend erythroleukemia. Recent work that demonstrated that gp55-dependent signaling activates the expression of Spi-1 even at early times during infection removes this complication (1 …”