The Antiapoptotic Gene mcl-1 Is Up-Regulated by the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway through a Transcription Factor Complex Containing CREB

• DOI: 10.1128/mcb.19.9.6195
• Publication Date: 2015-10-26T10:20:01Z
• Authors: Ju-Ming Wang; Jyh-Rong Chao; Wannhsin Chen; Min-Liang Kuo; Jeffrey J.-Y. Yen; Hsin-Fang Yang-Yen
• Keywords: 0301 basic medicine; Binding Sites; Base Sequence; Macromolecular Substances; Molecular Sequence Data; Granulocyte-Macrophage Colony-Stimulating Factor; Apoptosis; Protein Serine-Threonine Kinases; Cell Line; Neoplasm Proteins; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins; Humans; Myeloid Cell Leukemia Sequence 1 Protein; Interleukin-3; Cyclic AMP Response Element-Binding Protein; Promoter Regions, Genetic; Genes, Immediate-Early; Proto-Oncogene Proteins c-akt; DNA Primers

mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) signaling pathways plays important role in viability response of these cytokines. In this study, we demonstrated that cytokine stimulation mRNA protein expression were attenuated pretreatment cells with phosphatidylinositol 3-kinase (PI3-K) inhibitors. Reporter assays further showed PI3-K/Akt pathway was involved IL-3 activation transcription. Analysis promoter revealed both elements, SIE at position −87 CRE-2 −70, contribute to expression. Although either site or alone sufficient confer inducibility on a heterologous promoter, only reporter mediated via pathway. The binding activity constitutively high deprived stimulated IL-3. contrast, low cytokine-starved strongly induced within 1 h following treatment cells. addition, induction but not dependent Lastly, CREB one component complex played gene. Taken together, our results suggest PI3-K/Akt-dependent -independent Activation through transcription containing CREB.