Role of JunB in erythroid differentiation.

The role of junB as a regulator of erythroid cell survival, proliferation, and differentiation was tested by controlled expression of JunB in the erythropoietin (EPO)-dependent erythroleukemia cell line HCD57. JunB induced erythroid differentiation as evidenced by increased expression of the erythroid-specific proteins beta-globin, spectrin-alpha, and TER-119. Expression of JunB for at least 48 h was required for the differentiated phenotype to emerge. Differentiation was accompanied by a slower rate of proliferation and an increase in the expression of the cell cycle inhibitory protein p27. p27 protein expression increased due to reduced turnover without changes in transcription, indicating global changes in cell physiology following JunB induction. JunB expression was also studied in mouse and human primary erythroid cells. JunB expression increased immediately in both primary mouse cells and HCD57 cells treated with EPO and quickly returned to base-line levels, followed by a secondary rise in JunB in primary erythroid cells, but not in HCD57 cells, 36-48 h later. This result suggested that the initial EPO-dependent JunB induction was not sufficient to induce differentiation, but that the late EPO-independent JunB expression in primary erythroid cells was necessary for differentiation. This study suggests that JunB is an important regulator of erythroid differentiation.