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

structural homologies: they both contain two tandem caspase activation and recruitment
domains (CARD) at their N-terminus, and a DExD/H Box helicase domain at their C-
terminus. However, LGP2 only contains a DexD/H Box helicase domain. RIG-I has been
shown to recognize ssRNA bearing a 5’-triphosphate (Hornung et al., 2006; Pichlmair et
al., 2006) and short double strand RNAs, whilst MDA-5 recognizes long dsRNAs (Gitlin
et al., 2006) [For recent reviews, see (Meylan, Tschopp, and Karin, 2006; Takeuchi and
Akira, 2009; Wilkins and Gale, 2010)].
A common downstream signalling molecule shared by RIG-I and MDA-5 is MAVS (also
called IPS-1, VISA and Cardif) [(Hiscott et al., 2006; Kawai et al., 2005; Meylan et al.,
2005; Seth et al., 2005; Xu et al., 2005), reviewed by (Hiscott et al., 2006)]. MAVS is
localized at the outer mitochondria membrane by its C-terminal transmembrane domain,
and its N-terminal CARD domain is essential for mediating the interaction of RIG-I with
MAVS [reviewed in (Meylan, Tschopp, and Karin, 2006)]. The recruitment of MAVS by
RIG-I/MDA-5 leads to the transmembrane (TM)-dependent dimerization of MAVS and
subsequent recruitment and activation of the tumor necrosis factor (TNF) receptorassociated
factor (TRAF) family members, leading to signal transduction cascade and the
activation of transcription factors NF-κB and IRF-3, which are both essential components
for type I IFN induction (Baril et al., 2009).
1.1.1.2 IFN-β promoter
Induction of type I IFN requires the assembly of a higher order multi-component
transcription factor enhancer complex, termed the enhanceosome [reviewed by (Thanos,
3