Synergistic Activity of STAT3 and c-Jun at a Specific Array of DNA Elements in the α2-Macroglobulin Promoter

Joo Yeon Yoo, Wenlan Wang, Stephen Desiderio, Daniel Nathans

Research output: Contribution to journalArticle

Abstract

The transcriptional activity of natural promoters is sensitive to the precise spatial arrangement of DNA elements and their incorporation into higher order DNA-protein complexes. STAT3 and c-Jun form a specific ternary complex in vitro with a synthetic DNA element containing AP1 and SIE sites. These associations are critical for synergistic activation of transcription from a synthetic promoter by STAT3 and c-Jun. Expression of the acute phase protein α2-macroglobulin is induced in vivo by interleukin-6 (IL-6)-related cytokines; we demonstrate that coordinate interactions among STAT3, c-Jun, and a specific array of DNA elements contribute to activation of the α2-macroglobulin promoter in response to IL-6 family members. At least five promoter elements are involved in activation: two AP1 sites at -113 to -107 and -152 to -140, an acute phase response element (APRE (SIE)) at -171 to -163, and two AT-rich regions at -143 to -138 and -128 to -123. Synergism between STAT3 or STAT3-C and c-Jun is impaired by mutation of the APRE (SIE) or either AP1 site, as well as by mutations that alter the AT-rich regions or their phasing. Mutations of STAT3 previously shown to disrupt physical and functional interactions with c-Jun do not impair synergy between STAT3-C and c-Jun at the α2-macroglobulin promoter in HepG2 cells, suggesting that STAT3-C and STAT3 differ with respect to their precise contacts with c-Jun.

Original languageEnglish (US)
Pages (from-to)26421-26429
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number28
DOIs
StatePublished - Jul 13 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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