MEKK1 plays a critical role in activating the transcription factor C/EBP-β-dependent gene expression in response to IFN-γ

Sanjit K. Roy, Junbo Hu, Qingjun Meng, Ying Xia, Paul S. Shapiro, Sekhar P M Reddy, Leonidas C. Platanias, Daniel J. Lindner, Peter F. Johnson, Catrin Pritchard, Gilles Pagés, Jacques Pouyssegur, Dhananjaya V. Kalvakolanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

IFN-γ induces a number of genes to up-regulate cellular responses by using specific transcription factors and the cognate elements. We recently discovered that CCAAT/enhancer-binding protein-β (C/EBP-β) induces gene transcription through an IFN-response element called γ-IFN-activated transcriptional element (GATE). Using mutant cells, chemical inhibitors, and specific dominant negative inhibitors, we show that induction of GATE-driven gene expression depends on MEK1 (mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase) and ERKs (extracellular signal-regulated protein kinases) but is independent of Raf-1. Interestingly in cells lacking the MEKK1 gene or expressing the dominant negative MEKK1, ERK activation, and GATE dependent gene expression is inhibited. A dominant negative MEKK1 blocks C/EBP-β-driven gene expression stimulated by IFN-γ. These studies describe an IFN-γ-stimulated pathway that involves MEKK1-MEK1-ERK1/2 kinases to regulate C/EBP-β-dependent gene expression.

Original languageEnglish (US)
Pages (from-to)7945-7950
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number12
DOIs
StatePublished - Jun 11 2002

Keywords

  • Antiviral
  • Cell growth
  • Cytokines
  • Differentiation
  • Immune response

ASJC Scopus subject areas

  • General

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