A Unique SUMO-2-Interacting Motif within LANA Is Essential for KSHV Latency

PLoS Pathogens

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