Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA

Jin Gan, Chong Wang, Yanling Jin, Yi Guo, Feng Xu, Qing Zhu, Ling Ding, Hong Shang, Junwen Wang, Fang Wei, Qiliang Cai, Erle S. Robertson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 (LANASIM). In addition to the six bands identified as substantially associated with LANASIM, 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C-truncated mutants of LANA (LANANC), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs is associated with LANASIM. 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 LANASIM than the SUMO-1-modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANASIM 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 LANASIM-associated complex and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for Kaposi's sarcoma-associated herpesvirus persistence and pathogenesis.

Original languageEnglish (US)
Pages (from-to)2023-2037
Number of pages15
JournalProteomics
Volume15
Issue number12
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Human Herpesvirus 8
Proteomics
Sumoylation
Ubiquitin
Proteins
DNA Replication
Gene expression
Protein Isoforms
Viral Genes
DNA
RNA Precursors
Proteome
Nuclear Proteins
Chromatin
Cluster Analysis
latency-associated nuclear antigen
Cell Cycle
Carcinogenesis
Plasmids
Cells

Keywords

  • KSHV
  • LANA
  • Microbiology
  • SUMO-interacting motif

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Gan, J., Wang, C., Jin, Y., Guo, Y., Xu, F., Zhu, Q., ... Robertson, E. S. (2015). Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA. Proteomics, 15(12), 2023-2037. https://doi.org/10.1002/pmic.201400624

Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA. / 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.

In: Proteomics, Vol. 15, No. 12, 01.06.2015, p. 2023-2037.

Research output: Contribution to journalArticle

Gan, J, Wang, C, Jin, Y, Guo, Y, Xu, F, Zhu, Q, Ding, L, Shang, H, Wang, J, Wei, F, Cai, Q & Robertson, ES 2015, 'Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA', Proteomics, vol. 15, no. 12, pp. 2023-2037. https://doi.org/10.1002/pmic.201400624
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. / Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA. In: Proteomics. 2015 ; Vol. 15, No. 12. pp. 2023-2037.
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AU - Zhu, Qing

AU - Ding, Ling

AU - Shang, Hong

AU - Wang, Junwen

AU - Wei, Fang

AU - Cai, Qiliang

AU - Robertson, Erle S.

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AB - 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 (LANASIM). In addition to the six bands identified as substantially associated with LANASIM, 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C-truncated mutants of LANA (LANANC), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs is associated with LANASIM. 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 LANASIM than the SUMO-1-modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANASIM 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 LANASIM-associated complex and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for Kaposi's sarcoma-associated herpesvirus persistence and pathogenesis.

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