FIG. 10.

Model depicting the role of Fli-1 during proliferation and differentiation of erythroblasts. Epo induces downregulation of Fli-1 (↓) in HB60 cells, which results in terminal differentiation (see text). Upregulation of Fli-1 (↑) by ectopic expression (HB60-ED cells) and the addition of SCF, with or without Epo, to the culture of HB60 cells inhibits differentiation and promotes proliferation. These observations suggest the Fli-1 replaces the proliferative effect of SCF signaling in erythroblasts. Moreover, they indicate that Fli-1 functions as a switch mechanism which alters the responsiveness of erythroblast to undergo differentiation or proliferation by ectopic expression. This response is mediated through the regulation of several target genes. Rb is one of these target genes that is negatively regulated by Fli-1. High expression of Rb as a consequence of low Fli-1 could be one of the events involved in erythroid differentiation.