%0 Journal Article
%T A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency
%A Qiliang Cai
%A Shen Cai
%A Caixia Zhu
%A Suhbash C. Verma
%A Ji-Young Choi
%A Erle S. Robertson
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003750
%X Kaposi's sarcoma-associated herpesvirus (KSHV) stabilizes hypoxia-inducible factor ¦Á (HIF-1¦Á) during latent infection, and HIF-1¦Á reactivates lytic replication under hypoxic stress. However, the mechanism utilized by KSHV to block lytic reactivation with the accumulation of HIF-1¦Á in latency remains unclear. Here, we report that LANA encoded by KSHV contains a unique SUMO-interacting motif (LANASIM) which is specific for interaction with SUMO-2 and facilitates LANA SUMOylation at lysine 1140. Proteomic and co-immunoprecipitation analysis further reveal that the SUMO-2 modified transcription repressor KAP1 is a critical factor recruited by LANASIM. Deletion of LANASIM led to functional loss of both LANA-mediated viral episome maintenance and lytic gene silencing. Moreover, hypoxia reduced KAP1 SUMOylation and resulted in dissociation of both KAP1 and Sin3A repressors from LANASIM-associated complex. Therefore, the LANASIM motif plays an essential role in KSHV latency and is a potential drug target against KSHV-associated cancers.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003750