AI Article Synopsis

  • IFN-gamma activates gene expression by using specific transcription factors, including CCAAT/enhancer-binding protein-beta (C/EBP-beta), via a mechanism involving the gamma-IFN-activated transcriptional element (GATE).
  • The study reveals that C/EBP-beta's induction of gene transcription through GATE is reliant on the MEK1 and ERK signaling pathways, but does not involve Raf-1.
  • Additionally, the presence of MEKK1 is crucial for ERK activation and subsequent C/EBP-beta-driven gene expression in response to IFN-gamma, indicating a specific signaling cascade that regulates this process.

Article Abstract

IFN-gamma 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-beta (C/EBP-beta) induces gene transcription through an IFN-response element called gamma-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-beta-driven gene expression stimulated by IFN-gamma. These studies describe an IFN-gamma-stimulated pathway that involves MEKK1-MEK1-ERK1/2 kinases to regulate C/EBP-beta-dependent gene expression.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC123000PMC
http://dx.doi.org/10.1073/pnas.122075799DOI Listing

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