The junB gene is one of immediate-early genes whose expression are
regulated by a variety of extracellular stimuli and play important
roles in cellular responses to the given stimuli. Interleukin-6
(IL-6) activates the junB promoter through an IL-6 response element,
JRE-IL6, that is composed of two cooperative DNA motifs, a low
affinity Stat-binding site overlapping with an Ets-binding site
(JEBS) and a cAMP responsive element (CRE)-like site. This element is
a target for the Jak-Stat signal transduction pathway. We showed that
IL-6 induced novel complexes on JRE-IL6, termed JRE-IL6-BC1 and 2,
which contained Stat3 but migrated more slowly than the complexes
containing homo- or heterodimer of Stat3 and Stat1 in gel shift
assays. These slow-migrating JRE-IL6-BCs appeared to contain CRE-like
site binding proteins besides Stat3, since the formation of
JRE-IL6-BCs required both the JEBS and CRE-like site of JRE-IL6 and
oligonucleotides containing the CRE-like site or somatostatin CRE
efficiently competed with JRE-IL6 for making JRE-IL6-BCs. The
formation of the complexes correlated well with the responsiveness of
JRE-IL6 to IL-6 signals. U.v.-cross linking study revealed that
JRE-IL6 bound a 90 kDa protein, corresponding to Stat3, and a 36 kDa
protein, most likely a CRE-like site binding protein(s). Furthermore,
we showed that the IL-6/interferon gamma (IFN gamma) response element
in the IRF-1 promoter (IR/IRF-1), which contains a Stat-binding site
and an adjacent CRE-like site, also makes IL-6-induced binding
complexes similar to JRE-IL6-BCs.
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