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

1.1.3.6 ISG56
The ISG56 family of proteins are induced strongly in response to virus infection, IFNs
and dsRNA. In humans, this family comprises four members: ISG54, ISG56, ISG58 and
ISG60. In mice, this family comprises three members: ISG49, ISG54 and ISG56 (de Veer
et al., 1998; Lee et al., 1994; Levy et al., 1986). All of these proteins contain multiple
tetratricopeptide (TPR) motifs that are known to mediate protein-protein interactions
(Lamb, Tugendreich, and Hieter, 1995). ISG56 C-terminal region is responsible for
interaction with eIF3e subunit to impair the ability of eIF3 to stabilize the eIF2·GTP·MettRNA
i ternary complex (Guo et al., 2000; Hui et al., 2003a; Terenzi et al., 2006). Mouse
ISG54 and ISG56, as well as human ISG54, bind to eIF3c and eIF3e subunits to inhibit
protein translation (Hui et al., 2005; Terenzi et al., 2006; Terenzi, Pal, and Sen, 2005).
ISG56 was recently been reported to be an important antiviral molecule in IFN-induced
antiviral state, it was reported to inhibit hepatitis C virus (Sumpter et al., 2005), Sindbis
virus (Zhang et al., 2007), West Nile virus, lymphocytic choriomeningitis virus (LCMV)
(Wacher et al., 2007) and human papillomaviruses (HPV) (Terenzi, Saikia, and Sen,
2008). ISG56 exert its antiviral action against HPV by binding and translocating the
DNA replication origin-binding protein E1 of HPV from the nucleus to the cytoplasm,
thus mediating the inhibitory action of IFN on HPV DNA replication. Mutational studies
showed that the interaction is mediated by TRP repeat 2 (TRP2) of ISG56 and the C-
terminal region of E1 (Terenzi, Saikia, and Sen, 2008).
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