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 journalArticle

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

Fingerprint Dive into the research topics of 'MEKK1 plays a critical role in activating the transcription factor C/EBP-β-dependent gene expression in response to IFN-γ'. Together they form a unique fingerprint.

  • Cite this

    Roy, S. K., Hu, J., Meng, Q., Xia, Y., Shapiro, P. S., Reddy, S. P. M., Platanias, L. C., Lindner, D. J., Johnson, P. F., Pritchard, C., Pagés, G., Pouyssegur, J., & Kalvakolanu, D. V. (2002). MEKK1 plays a critical role in activating the transcription factor C/EBP-β-dependent gene expression in response to IFN-γ. Proceedings of the National Academy of Sciences of the United States of America, 99(12), 7945-7950. https://doi.org/10.1073/pnas.122075799