Signaling pathways to the assembly of the interferon-b enhanceosome: chemical genetic studies with a small molecule.

kim / t. / kim / t.y. / lee / w.g. / yim / j. / kim / t.k.researcher
Small molecules that modulate specific protein functions are valuable tools for dissecting complex signaling pathways. Here, we identified a small molecule that induces the assembly of the interferon-beta (IFN-beta) enhanceosome by stimulating all the enhancer-binding activator proteins: ATF2/c-JUN, IRF3, and p50/p65 of NF-kappa B. This compound stimulates mitogen-activated protein kinase kinase kinase 1 (MEKK1), which is a member of a family of proteins involved in stress-mediated signaling pathways. Consistent with this, MEKK1 activates IRF3 in addition to ATF2/c-JUN and NF-kappa B for the assembly of the IFN-beta enhanceosome. MEKK1 activates IRF3 through the c-JUN amino-terminal kinase (JNK) pathway but not the p38 and I kappa B kinase (IKK) pathway. Taken together with previous observations, these results implicate that, for the assembly of an IFN-beta enhanceosome, MEKK1 can induce IRF3 and ATF2/c-JUN through the JNK pathway, whereas it can induce NF-kappa B through the IKK pathway. Thus, specific MEKK family proteins may be able to integrate some of multiple signal transduction pathways leading to the specific activation of the IFN-beta enhanceosome.
Publisher
Amer Soc Biochemistry Molecular Biology Inc
Issue Date
2000-06
Language
ENG
Keywords

NF-KAPPA-B; REGULATORY FACTOR-3; TRANSCRIPTIONAL SYNERGY; MEK KINASE-1; DNA-DAMAGE; IN-VITRO; ACTIVATION; PROTEIN; P53; TRANSDUCTION

Citation

JOURNAL OF BIOLOGICAL CHEMISTRY, v.275, no.22, pp.16910 - 16917

ISSN
0021-9258
DOI
10.1074/jbc.M000524200
URI
http://hdl.handle.net/10203/73162
Appears in Collection
BS-Journal Papers(저널논문)
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