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activity specific for the yeast MAPK Ste7. Indeed, in yeast cells IpaH9.8 inter-
rupts pheromone response signaling by promoting the proteasome-dependent
destruction of Ste7 ( Rohde et al., 2007 ) and replacement of an invariant Cys
residue abolished the ubiquitin ligase activity of IpaH9.8 ( Rohde et al., 2007 ).
More recently IpaH9.8 has been shown to dampen the host NF-κB-mediated
inflammatory response in mammalian cells ( Ashida et al., 2010 ). IpaH9.8 inter-
acts directly with NEMO/IKKγ and ABIN-1, an ubiquitin adaptor protein, pro-
moting ABIN-1-dependent polyubiquitination of NEMO on two specific Lys
residues (K309 and K321). Consequently, polyubiquitinated NEMO undergoes
proteasome-dependent degradation and blocks NF-κB activation ( Ashida et al.,
2010 ).
OspF, another T3SS effector of Shigella , is translocated into the host cell
nucleus, where it targets components of the MAPK pathway ( Arbibe et al.,
2007 ). OspF has a phosphothreonine lyase activity, which mediates irrevers-
ible dephosphorylation of MAPKs thereby inactivating them. This irreversible
modification inhibits the downstream phosphorylation of histone H3 at Ser10
and ultimately results in the inhibition of transcriptional activation of NF-κB-
regulated genes, including IL-8 ( Arbibe et al., 2007 ; Kramer et al., 2007 ; Li
et al., 2007 ; Zurawski et al., 2009 ).
OspI was recently identified as a new T3SS effector of Shigella that selec-
tively deamidates a glutamine residue to glutamic acid in the E2 enzyme
UBC13. This modification abolishes UBC13 E2 ubiquitin-conjugating activity
required for the activation and polyubiquitylation of TRAF6. The authors also
demonstrated that through OspI activity, Shigella can block NF-κB-mediated
inflammatory response at an early stage of epithelial invasion ( Sanada et al.,
2012 ). Indeed, OspI encoding gene (orf169b) was initially identified because
its mutation led to a dramatic increase in the expression of pro-inflammatory
chemokines and cytokines in HeLa-infected cells at early stages of infection.
Although the impact of OspI activity on NF-κB pathway was clearly demon-
strated, it still remains to be elucidated whether by abolishing TRAF6 activation
OspI can also influence MAPKs mediated signaling pathways.
Escape from autophagy
Autophagy is an evolutionarily conserved catabolic pathway that allows
eukaryotes to degrade proteins and organelles by sequestering them in special-
ized double-membrane vesicles named autophagosomes ( Levine et al., 2008;
Yang et al., 2010 ). Although autophagosomes can sequester cytosolic material
non-specifically, selective autophagy mediates degradation of various cellular
structures, including protein aggregates, mitochondria, and invading microbes
tagged by ubiquitin molecules ( Kirkin et al., 2009 ; Kraft et al., 2010 ; Johansen
and Lamark, 2011 ). Autophagic receptors (p62 and NDP52) can simultaneously
bind ubiquitin and the autophagosome-associated ubiquitin-like proteins (i.e.
LC3/GABARAP proteins) thus mediating docking of ubiquitinated cargo to
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