mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response

Jyh Rong Chao, Ju Ming Wang, Shern Fwu Lee, Hsien Wei Peng, Yi Hung Lin, Chiang Hung Chou, Jian Chiuan Li, Huei Mei Huang, Chen Kung Chou, Min Liang Kuo, Jeffrey J Y Yen, Hsin Fang Yang-Yen

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Abstract

mcl-1, a bcl-2 family member, was originally identified as an early gene induced during differentiation of ML-1 myeloid leukemia cells. In the present study, we demonstrate that Mcl-1 is tightly regulated by the granulocyte- macrophage colony-stimulating factor (GM-CSF) signaling pathway. Upon deprivation of survival factor from TF-1 myeloid progenitor cells, Mcl-1 levels quickly dropped prior to visible detection of apoptosis of these cells. Upon restimulation of these deprived cells with GM-CSF, the mcl-1 mRNA was immediately induced and its protein product was accordingly resynthesized. Analysis with Ba/F3 cells expressing various truncation mutants of the GM-CSF receptor revealed that the membrane distal region between amino acids 573 and 755 of the receptor β chain was required for mcl-1 induction. Transient-transfection assays with luciferase reporter genes driven by various regions of the mcl-1 promoter demonstrated that the upstream sequence between -197 and -69 is responsible for cytokine activation of the mcl-1 gene. Overexpression of mcl-1 delayed but did not completely prevent apoptosis of cells triggered by cytokine withdrawal. Its down regulation by antisense constructs overcame, at least partially, the survival activity of GM-CSF and induced the apoptosis of TF-1 cells. Taken together, these results suggest that mcl-1 is an immediate-early gene activated by the cytokine receptor signaling pathway and is one component of the GM-CSF viability response.

Original languageEnglish
Pages (from-to)4883-4898
Number of pages16
JournalMolecular and Cellular Biology
Volume18
Issue number8
Publication statusPublished - Aug 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Chao, J. R., Wang, J. M., Lee, S. F., Peng, H. W., Lin, Y. H., Chou, C. H., Li, J. C., Huang, H. M., Chou, C. K., Kuo, M. L., Yen, J. J. Y., & Yang-Yen, H. F. (1998). mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Molecular and Cellular Biology, 18(8), 4883-4898.