Characterization of a cell-type-restricted negative regulatory activity of the human granulocyte-macrophage colony-stimulating factor gene

John K. Fraser, Juan J. Guerra, Chi Y. Nguyen, Jeffrey E. Indes, Judith C. Gasson, Stephen D. Nimer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of normal myeloid progenitor cells and can also stimulate the growth of acute myelogenous leukemia (AML) blasts. GM-CSF is not normally produced by resting cells but is expressed by a variety of activated cells including T lymphocytes, macrophages, and certain cytokine- stimulated fibroblasts and endothelial cells. Production of GM-CSF by cultured AML cells has been demonstrated, and GM-CSF expression by normal myeloid progenitors has been postulated to play a role in myelopoiesis. We have investigated the regulation of expression of GM-CSF in AML cell lines, and our results demonstrate the presence of a strong constitutive promoter element contained within 53 bp upstream of the cap site. We have also identified a negative regulatory element located immediately upstream of the positive regulatory element (within 69 bp of the cap site) that is active in AML cell lines but not T cells or K562 CML cells. Competition transfection and mobility shift studies demonstrate that this activity correlates with binding of a 45-kDa protein.

Original languageEnglish (US)
Pages (from-to)2213-2221
Number of pages9
JournalMolecular and cellular biology
Volume14
Issue number3
DOIs
StatePublished - Mar 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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