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Proteomic profiling identifies the SIM‐associated complex of KSHV‐encoded LANA
Author(s) -
Gan Jin,
Wang Chong,
Jin Yanling,
Guo Yi,
Xu Feng,
Zhu Qing,
Ding Ling,
Shang Hong,
Wang Junwen,
Wei Fang,
Cai Qiliang,
Robertson Erle S.
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400624
Subject(s) - sumo protein , biology , kaposi's sarcoma associated herpesvirus , chromatin , nuclear protein , gene silencing , heterochromatin , gene , microbiology and biotechnology , genetics , ubiquitin , transcription factor , virus , viral disease , herpesviridae
The Kaposi's sarcoma‐associated herpesvirus (KSHV) encoded latent nuclear antigen latency‐associated nuclear antigen (LANA) plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation, which results in chromatin silencing. To examine the pleiotropic effects of LANA protein on host cell gene expression, we utilized MS analysis to identify cellular proteins associated with the small ubiquitin related modifier (SUMO) interacting motif of LANA (LANA SIM ). In addition to the six bands identified as substantially associated with LANA SIM , 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N‐ and C‐truncated mutants of LANA (LANA NC ), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs is associated with LANA SIM . Intriguingly, consistent with our previous report that identified KAP1 as a key component, the in vitro SUMO‐2‐modified isoform has a substantially higher affinity with LANA SIM than the SUMO‐1‐modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANA SIM regulatory circuit involving aberrant SUMOylation of cell cycle (particular mitotic), DNA unwinding and replication, and pre‐mRNA/mRNA processing related proteins. This study provides a SUMOylated and non‐SUMOylated proteome profile of LANA SIM ‐associated complex and facilitates our understanding that viral‐mediated gene regulation through SUMOylation is important for Kaposi's sarcoma‐associated herpesvirus persistence and pathogenesis.