Biology Reference
In-Depth Information
Fig. 5
Schematic representation of the pUL84 NLS/importin-α binding domain. The localization
of the two autonomous leucine-rich nuclear export signals within the NLS domain is shown on
gray background
. Leucine residues with a critical function for the nuclear export activity are
underlined
may depend on protein dimerization generates the functional pUL84 NLS (Lischka
et al. 2003a).
Interestingly, sequence inspection of the UL84-importin-α interaction domain
revealed the presence of two small leucine-rich regions that exactly match the
consensus sequence of a classical nuclear export signal, suggesting that the pUL84
NLS domain may also be able to mediate nuclear export, thus serving as a complex
bidirectional transport domain (Fig. 5). Further experimentation revealed that both
leucine-rich regions are able to function as autonomous nuclear export signals and
are required for CRM-1 dependent nucleocytoplasmic shuttling of pUL84 (Lischka
et al. 2006a). This suggests that pUL84, in addition to its role within the nucleus as
an initiator protein of origin-dependent viral DNA replication, may carry out an
unexpected function within the cytoplasm that has yet to be defined. However,
given the recent description of a sequence-specific RNA-binding activity of pUL84
(Colletti et al. 2007) as well as its homology to DExD/H box RNA helicases
(Colletti et al. 2005), it is tempting to speculate that pUL84, similar to the UL69
protein, may be able to enhance the accumulation of specific viral transcripts within
the cytoplasm of infected cells.
Unconventional Interactions with the Nuclear Transport
Machinery: Novel Targets for Antiviral Strategies?
Recent reports emphasize that drug action and delivery can take advantage of
cellular compartmentation instead of simply blocking enzymatic active sites, thus
suggesting that the interference with nucleocytoplasmic shuttling may be a promis-
ing target for novel drug development (Gasiorowski and Dean 2003). A well-studied
example where such a strategy has already been used for therapeutic intervention is
