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-kappaB. 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-kappaB 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 IkappaB 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-kappaB 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.