Biology Reference
In-Depth Information
proteins interact with the RNA component of ribonucleoproteins, unwind RNA,
shuttle RNA from the nucleus to the cytoplasm, can either up- or downregulate
certain promoters, and can directly and actively displace stably bound proteins from
RNA (Fairman et al. 2004; Jankowsky and Bowers 2006). There is overwhelming
functional evidence that UL84 performs many of the activities similar to those
described for DExH/D Box proteins. One of the most interesting features of UL84,
mentioned above, also consistent with DExH/D Box protein activity, is that it was
shown to shuttle between the nucleus and the cytoplasm (Lischka et al. 2006). This
activity serves presumably to increase the accumulation of mRNA in the cytoplasm,
although no substrate RNAs were identified. This novel shuttling property of UL84
suggests that UL84 can function in some as yet undefined role in the cytoplasm.
This role may involve the export of viral or cellular encoded RNA in order to
increase the steady state level of an essential protein.
Viral and Cellular Encoded UL84 Binding Partners
Although it is known that UL84 interacts with IE2, other binding partners have
been identified. Our laboratory has performed a proteomics analysis to identify
other potential binding partners for UL84 in infected cells. This analysis identified
HCMV UL44 and UL83 (pp65) as viral encoded factors that interact with UL84
(Y. Gao et al., 2008). Our analysis also identified CK2 alpha and beta subunits, as
well as the cellular protein importin. These results are interesting in that this is the
first time that UL84 has been shown to interact with a member of the viral DNA
replication machinery as well as a protein (pp65) that is a component of the virion.
Additionally, although it was previously reported that UL84 is phosphorylated in
infected cells, this result strongly suggests that UL84 is a substrate for casein kinase
II (CK2).
Another interesting finding from the proteomics analysis is that UL84 is ubiqui-
tinated in infected cells. This was also discovered in the proteomics analysis of
UL84, which revealed two protein spots for UL84 in the 2D gel. Although molecu-
lar weights of these two UL84 protein species varied only slightly, their respective
pI indicated that one was more acidic than the other. Protein sequence data from
one UL84 spot showed that ubiquitin E2-conjugating enzyme was also present.
Further analysis using the proteosome inhibitor MG132 demonstrated that UL84
was monoubiquitinated. This apparent mono ubiquitination implicates UL84 as a
factor that may influence the degradation of other proteins or may be involved in a
multistep regulated degradation pathway.
The interaction of UL84 with UL44 (Pol accessory protein) is very interesting
in that the initiator protein for herpes simplex virus type 1 (HSV-1), UL9, also
interacts with its Pol accessory protein (Trego and Parris 2003). It is postulated that
UL42 increases the ability of UL9 to load on DNA (Trego et al. 2005), a scenario
that is also plausible for UL84 with respect to its interaction with UL44. The find-
ing that UL44 interacts with UL84 opens up the possibility that UL44 may have a
