Reciprocal effects of C/EBPα and PKCδ on JunB expression and monocytic differentiation depend upon the C/EBPα basic region

Huaitian Liu, Jeffrey R. Keefer, Qian Fei Wang, Alan D. Friedman

Research output: Contribution to journalArticle

Abstract

Monocytic differentiation of 32DPKCδ cells in response to activation of protein kinase C δ (PKCδ) by phorbol 12-myristate 13-acetate (PMA) was inhibited by exogenous CCAAT/ enhancer binding protein α-estradiol receptor (C/EBPα-ER), which impeded morphologic maturation and induction of macrosialin mRNA. Inhibition of monopoiesis was also evident in 32DPKCδ subclones expressing C/EBPαLeu12Val-ER, which cannot dimerize or bind DNA because of mutation of the leucine zipper, C/EBPαGZ-ER, in which the leucine zipper has been replaced by the GCN4 zipper, or C/EBPαΔ38-ER, lacking the C/EBPα transactivation domains. In contrast, C/EBPαBR3-ER, containing a mutant basic region, did not inhibit monocytic differentiation. C/EBPα-ER strongly inhibited endogenous AP-1 DNA-binding. Supershift analysis revealed that the major AP-1 complex contains JunB. Activation of C/EBPα-ER specifically reduced endogenous JunB RNA and protein and exogenous JunB levels without affecting endogenous or exogenous c-Jun. The stability of PMA-induced JunB was not affected. Thus, C/EBPα-ER suppresses both JunB transcription and posttranscriptional protein generation or induction. PU.1 levels and activity were increased. The Leu12Val, GZ, and Δ3-8 mutants also inhibited JunB expression, whereas the BR3 mutant was ineffective, indicating that inhibition of JunB expression and monocytic differentiation by C/EBPα-ER depends upon an interaction mediated by its basic region. Exogenous JunB restored AP-1 DNA-binding but did not prevent inhibition of macrosialin expression by C/EBPα-ER, indicating that JunB is not the only target relevant to inhibition of monopoiesis by C/EBPα.

Original languageEnglish (US)
Pages (from-to)3885-3892
Number of pages8
JournalBlood
Volume101
Issue number10
DOIs
StatePublished - May 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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