Han Xiao PhD thesis - Research@StAndrews:FullText - University of ...

1996)]. The IFN-β promoter consists of a set of cis regulatory elements designated
positive regulatory domains (PRDs). PRDIV, PRD I/III and PRD II are recognized by
activating transcription factor 2 (ATF-2)/C-Jun, IFN regulatory factors (IRFs), and NFκB
respectively. These trans elements, together with the architectural protein non-histone
high mobility group HGM I(Y), form the enhanceosome (Falvo, Thanos, and Maniatis,
1995; Thanos and Maniatis, 1995). The cooperative assembly of the enhanceosome not
only facilitates the binding of activators to promoter regions, but also stabilizes the
interaction with basal transcription machinery to activate IFN-β gene transcription (Fig.
1.2).
All of these trans activators need to be phosphorylated by cellular kinases from the signal
transmitted from RLRs/MAVS signalling pathway. NF-κB is normally held in a
quiescent state in the cytoplasm by association with an inhibitory molecule IκB. The
associated IκB masks the NF-κB nuclear localization signal (NLS) and thereby inhibits
its nuclear translocation. Upon stimulation of a varity of stress signals, IκB is
phosphorylated and targeted by proteasomal degradation thus leading to NF-κB nuclear
translocation [reviewed in (Israel, 2000)]. IFN regulatory factor 3 (IRF-3) is
constitutively expressed inside the cells and mainly localized in the cytoplasm. Upon
virus infection, IRF-3 is hyperphosphorylated on a number of serine and threonine
residues at its C-terminus, leading to its dimerization and translocation into the nucleus
(Kumar et al., 2000).
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