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A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency
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نویسنده
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cai q. ,cai s. ,zhu c. ,verma s.c. ,choi j.-y. ,robertson e.s.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 11
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چکیده
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Kaposi's sarcoma-associated herpesvirus (kshv) stabilizes hypoxia-inducible factor α (hif-1α) during latent infection,and hif-1α reactivates lytic replication under hypoxic stress. however,the mechanism utilized by kshv to block lytic reactivation with the accumulation of hif-1α 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. © 2013 cai et al.
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آدرس
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moe and moh key laboratory of medical molecular virology,school of basic medical science,shanghai medical college,fudan university,shanghai,china,department of microbiology and abramson comprehensive cancer center,perelman school of medicine at the university of pennsylvania,philadelphia, United States, moe and moh key laboratory of medical molecular virology,school of basic medical science,shanghai medical college,fudan university,shanghai, China, moe and moh key laboratory of medical molecular virology,school of basic medical science,shanghai medical college,fudan university,shanghai, China, department of microbiology and immunology,school of medicine university of nevada,reno,nv, United States, department of microbiology and abramson comprehensive cancer center,perelman school of medicine at the university of pennsylvania,philadelphia, United States, department of microbiology and abramson comprehensive cancer center,perelman school of medicine at the university of pennsylvania,philadelphia, United States
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Authors
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