Interleukin 3-dependent activation of DREAM is involved in transcriptionalsilencing of the apoptotic hrk gene in hematopoietic progenitor cells

The apoptotic protein Hrk is expressed in hematopoietic progenitors after g rowth factor deprivation Here we identify a silencer sequence in the 3' unt ranslated region of the hrk gene tat binds to the transcriptional repressor DREAM in interleukin-3 (IL-3)-dependent hematopoietic progenitor cells, an d abrogates the expression of reporter genes when located downstream of the open reading frame. In addition, the binding of DREAM to the hrk gene is r educed or eliminated when cells are cultured in the absence of IL-3 or trea ted with a calcium ionophore or a phosphatidylinositol 3-kinase-specific in hibitor, suggesting that both calcium mobilization and phosphorylation can regulate the transcriptional activity of DREAM, Furthermore, we have shown that DREAM is phosphorylated by a phosphatidylinositol 3-kinase-dependent, but Akt-independent pathway. In all cases, loss of the DREAM-DNA binding co mplex was correlated with increased levels of Hrk and apoptosis These data suggest that IL-3 may trigger the activation of DREAM through different sig naling pathways, which in turn binds to a silencer sequence in the hrk gene and blacks transcription, avoiding inappropriate cell death in hematopoiet ic progenitors.