Regulation of granulocyte and monocyte differentiation by CCAAT/enhancer binding protein α

Alan David Friedman, Jeffrey Keefer, Tanawan Kummalue, Huaitian Liu, Qian Fei Wang, Rebecca Cleaves

Research output: Contribution to journalArticle

Abstract

CCAAT/enhancer binding protein α (C/EBPα)-ER induces 32Dcl3 neutrophilic differentiation and inhibits 32DPKCδ maturation to macrophages in response to phorbol ester. In 32Dcl3 cells, C/EBPα-ER rapidly induces the PU.1 and C/EBPα RNAs even in the presence of cycloheximide, suggesting that these are direct C/EBPα genetic targets. C/EBPα strongly binds and modestly activates the murine PU.1 promoter via an evolutionarily conserved binding site. C/EBPα-ER variants incapable of binding DNA still slow G1 progression but do not induce differentiation. N-terminally truncated C/EBPα variants, including the p30 isoform expressed in a subset of AMLs, also retain the ability to slow 32D cl3 proliferation, whereas the C/EBPα(BRM2)-ER variant does not slow G1 progression, has a reduced capacity to induce early granulocytic markers, and does not induce terminal maturation. In 32DPKCδ cells, C/EBPα-ER strongly inhibits endogenous or exogenous JunB induction, dependent upon the outer surface of the C/EBPα basic region, but does not inhibit c-Jun, PU.1, or C/EBPβ expression. Exogenous JunB restores AP-1 DNA binding but does not overcome inhibition of monopoiesis by C/EBPα-ER. In summary, we propose that while C/EBPα is required for development of immature granulocyte-monocyte progenitors, C/EBPα subsequently inhibits monopoiesis, via inhibition of JunB express and via additional activities, and induces granulopoiesis, via induction of PU.1, C/EBPε, and cell cycle arrest.

Original languageEnglish (US)
Pages (from-to)338-341
Number of pages4
JournalBlood Cells, Molecules, and Diseases
Volume31
Issue number3
DOIs
StatePublished - Nov 2003

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CCAAT-Enhancer-Binding Proteins
Granulocytes
Monocytes
Granulocyte Precursor Cells
DNA
Transcription Factor AP-1
Phorbol Esters
Cycloheximide

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

Regulation of granulocyte and monocyte differentiation by CCAAT/enhancer binding protein α. / Friedman, Alan David; Keefer, Jeffrey; Kummalue, Tanawan; Liu, Huaitian; Wang, Qian Fei; Cleaves, Rebecca.

In: Blood Cells, Molecules, and Diseases, Vol. 31, No. 3, 11.2003, p. 338-341.

Research output: Contribution to journalArticle

Friedman, Alan David ; Keefer, Jeffrey ; Kummalue, Tanawan ; Liu, Huaitian ; Wang, Qian Fei ; Cleaves, Rebecca. / Regulation of granulocyte and monocyte differentiation by CCAAT/enhancer binding protein α. In: Blood Cells, Molecules, and Diseases. 2003 ; Vol. 31, No. 3. pp. 338-341.
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