PLoS Pathogens | |
A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency | |
Erle S. Robertson1  Shen Cai1  Ji-Young Choi2  Suhbash C. Verma3  Qiliang Cai3  Caixia Zhu3  | |
[1] Department of Microbiology and Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States of America;Department of Microbiology and Immunology, School of Medicine University of Nevada, Reno, Nevada, United States of America;MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China | |
关键词: SUMOylation; Hypoxia; Immunoprecipitation; Sequence motif analysis; Lysine; Immunoblotting; Kaposi's sarcoma-associated herpesvirus; DNA-binding proteins; | |
DOI : 10.1371/journal.ppat.1003750 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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RO201902018892512ZK.pdf | 4150KB | download |