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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Lytic Replication Abstract 37
NOVEL FUNCTIONS OF K-RTA AND K-BZIP AS SUMO-TARGETING LIGASES AND
EPIGENETIC REGULATORS
Hsing-Jien Kung, Pei-Ching Chang, Latricia Fitzgerald, Tom Ellison, Paul Luciw* and Yoshi
Izumiya
Dept. of Biochemistry and Molecular Medicine, *Dept of Pathology, UC Davis Cancer
Center, Sacramento CA 95864
Abstract
SUMO modification emerges as a major post-translational modification of viral and
cellular proteins. Sumoylation in concert with histone methylation at H3K9 are hallmarks
of heterochromatin. Like phospho-tyrosines, sumoylated lysines also serve as signals
linking components of signal transduction. SUMO interacting motifs (SIM) have been
identified in a number of cellular regulatory proteins including PML, DAXX and RNF4.
RNF4, a SUMO-targeting ubiquitin ligase, preferentially facilitates the degradation of
sumoylated proteins. Here we report the identification of K-Rta and K-bZIP as SUMO
binding proteins, and have mapped the SIMs in these molecules. We have previously
shown that K-bZIP behaves like a SUMO-ligase, via its ability to bind Ubc9 E2 SUMO
conjugation enzyme (which is itself sumoylated). Studies from the labs of Hayward and
Wood showed that K-Rta behaves like a ubiquitin ligase. We reported that K-Rta
decreases the overall level of sumoylated proteins, and is counteracted by K-bZIP. We
now show that K-Rta preferentially degrades sumoylated interacting protein. Taken in the
present context, these data are consistent with the notion that K-bZIP is a SUMOtargeting
SUMO ligase, and K-Rta, a SUMO-targeting Ubiquitin ligase. If true, they are
the first SUMO-targeting viral ligases identified. The ability of K-Rta and K-bZIP to
modulate the activity and stability of sumoylated proteins raises the possibility of their
roles in the epigenetic regulation of viral latency. Data will be presented that JMJD2A, a
H3K9me3 histone demethylase, is sumoylated and its demethylase activity is directly
blocked by K-bZIP.
Presenting author Email: yizumiya@ucdavis.edu
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