PU.1 is a member of Ets family of transcription factors, some of which play critical roles in cell growth and development of hematopoietic cells in cooperation with other transcription factors and cofactors. We previously reported that overexpression of PU.1 in murine erythroleukemia (MEL) cells results in growth inhibition, differentiation block and apoptotic cell death in conjunction with DMSO or HMBA treatment. We also showed that PU.1 interacts with the transcriptional co-activator CREB binding protein (CBP). In this study, we have investigated whether CBP is involved in PU.1-induced growth inhibition, differentiation block and apoptosis in MEL cells. Overexpression of CBP rescued MEL cells from PU.1-induced growth inhibition and apoptosis, while it did not release the cells from PU.1-induced block of erythroid differentiation. These results suggest that sequestration of CBP is involved in PU.1-induced growth inhibition and apoptosis but not differentiation block in MEL cells. These results also suggest that the molecular mechanisms on PU.1-induced growth inhibition and apoptosis are different from the mechanism on PU.1-induced differentiation block in MEL cells.