The Med1 subunit of transcriptional mediator plays a central role in regulating CCAAT/enhancer-binding protein-β-driven transcription in response to interferon-γ

Hui Li, Padmaja Gade, Shreeram C. Nallar, Abhijit Raha, Sanjit K. Roy, Sreenivasu Karra, Janardan K. Reddy, Sekhar P. Reddy, Dhananjaya V. Kalvakolanu

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Transcription factor CCAAT/enhancer-binding protein (C/EBP)-β is crucial for regulating transcription of genes involved in a number of diverse cellular processes, including those involved in some cytokine-induced responses. However, the mechanisms that contribute to its diverse transcriptional activity are not yet fully understood. To gain an understanding into its mechanisms of action, we took a proteomic approach and identified cellular proteins that associate with C/EBP-β in an interferon (IFN)-γ-dependent manner. Transcriptional mediator (Mediator) is a multisubunit protein complex that regulates signal-induced cellular gene transcription from enhancer-bound transcription factor(s). Here, we report that the Med1 subunit of the Mediator as a C/EBP-β-interacting protein. Using gene knock-out cells and mutational and RNA interference approaches, we show that Med1 is critical for IFN-induced expression of certain genes. Med1 associates with C/EBP-β through a domain located between amino acids 125 and 155 of its N terminus. We also show that the MAPK, ERK1/2, and an ERK phosphorylation site within regulatory domain 2, more specifically the Thr189 residue, of C/EBP-β are essential for it to bind to Med1. Last, an ERK-regulated site in Med1 protein is also essential for up-regulating IFN-induced transcription although not critical for binding to C/EBP-β.

Original languageEnglish (US)
Pages (from-to)13077-13086
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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