Analysis of the SUMO2 Proteome during HSV-1 Infection

Elizabeth Sloan, Michael Tatham, Marie Groslambert, Mandy Glass, Anne Orr, Ron T Hay, Roger D Everett

Research output: Contribution to journalArticle

Abstract

Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expression, chromatin structure, nuclear transport and RNA metabolism. Sumoylation is also linked, both positively and negatively, with the replication of many different viruses both in terms of modification of viral proteins and modulation of sumoylated cellular proteins that influence the efficiency of infection. One prominent example of the latter is the widespread reduction in the levels of cellular sumoylated species induced by herpes simplex virus type 1 (HSV-1) ubiquitin ligase ICP0. This activity correlates with relief from intrinsic immunity antiviral defence mechanisms. Previous work has shown that ICP0 is selective in substrate choice, with some sumoylated proteins such the promyelocytic leukemia protein PML being extremely sensitive, while RanGAP is completely resistant. Here we present a comprehensive proteomic analysis of changes in the cellular SUMO2 proteome during HSV-1 infection. Amongst the 877 potentially sumoylated species detected, we identified 124 whose abundance was decreased by a factor of 3 or more by the virus, several of which were validated by western blot and expression analysis. We found many previously undescribed substrates of ICP0 whose degradation occurs by a range of mechanisms, influenced or not by sumoylation and/or the SUMO2 interaction motif within ICP0. Many of these proteins are known or are predicted to be involved in the regulation of transcription, chromatin assembly or modification. These results present novel insights into mechanisms and host cell proteins that might influence the efficiency of HSV-1 infection.
Original languageEnglish
Article numbere1005059
JournalPLOS Pathogens
Volume11
Issue number7
DOIs
Publication statusPublished - 22 Jul 2015
Externally publishedYes

Fingerprint

Human Herpesvirus 1
Virus Diseases
Proteome
Viruses
Sumoylation
Ubiquitin
Proteins
Small Ubiquitin-Related Modifier Proteins
Transcription
Nuclear RNA
Chromatin Assembly and Disassembly
Cell Nucleus Active Transport
Protein Stability
Chromatin
Gene Expression Regulation
Viral Proteins
Ligases
Proteomics
Antiviral Agents
Immunity

Keywords

  • SUMO
  • proteome
  • virus
  • HSV-1

Cite this

Sloan, E., Tatham, M., Groslambert, M., Glass, M., Orr, A., Hay, R. T., & Everett, R. D. (2015). Analysis of the SUMO2 Proteome during HSV-1 Infection. PLOS Pathogens, 11(7), [e1005059]. https://doi.org/10.1371/journal.ppat.1005059
Sloan, Elizabeth ; Tatham, Michael ; Groslambert, Marie ; Glass, Mandy ; Orr, Anne ; Hay, Ron T ; Everett, Roger D. / Analysis of the SUMO2 Proteome during HSV-1 Infection. In: PLOS Pathogens. 2015 ; Vol. 11, No. 7.
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Sloan, E, Tatham, M, Groslambert, M, Glass, M, Orr, A, Hay, RT & Everett, RD 2015, 'Analysis of the SUMO2 Proteome during HSV-1 Infection', PLOS Pathogens, vol. 11, no. 7, e1005059. https://doi.org/10.1371/journal.ppat.1005059

Analysis of the SUMO2 Proteome during HSV-1 Infection. / Sloan, Elizabeth; Tatham, Michael; Groslambert, Marie; Glass, Mandy; Orr, Anne; Hay, Ron T; Everett, Roger D.

In: PLOS Pathogens, Vol. 11, No. 7, e1005059, 22.07.2015.

Research output: Contribution to journalArticle

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AU - Sloan, Elizabeth

AU - Tatham, Michael

AU - Groslambert, Marie

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AU - Hay, Ron T

AU - Everett, Roger D

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AB - Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expression, chromatin structure, nuclear transport and RNA metabolism. Sumoylation is also linked, both positively and negatively, with the replication of many different viruses both in terms of modification of viral proteins and modulation of sumoylated cellular proteins that influence the efficiency of infection. One prominent example of the latter is the widespread reduction in the levels of cellular sumoylated species induced by herpes simplex virus type 1 (HSV-1) ubiquitin ligase ICP0. This activity correlates with relief from intrinsic immunity antiviral defence mechanisms. Previous work has shown that ICP0 is selective in substrate choice, with some sumoylated proteins such the promyelocytic leukemia protein PML being extremely sensitive, while RanGAP is completely resistant. Here we present a comprehensive proteomic analysis of changes in the cellular SUMO2 proteome during HSV-1 infection. Amongst the 877 potentially sumoylated species detected, we identified 124 whose abundance was decreased by a factor of 3 or more by the virus, several of which were validated by western blot and expression analysis. We found many previously undescribed substrates of ICP0 whose degradation occurs by a range of mechanisms, influenced or not by sumoylation and/or the SUMO2 interaction motif within ICP0. Many of these proteins are known or are predicted to be involved in the regulation of transcription, chromatin assembly or modification. These results present novel insights into mechanisms and host cell proteins that might influence the efficiency of HSV-1 infection.

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Sloan E, Tatham M, Groslambert M, Glass M, Orr A, Hay RT et al. Analysis of the SUMO2 Proteome during HSV-1 Infection. PLOS Pathogens. 2015 Jul 22;11(7). e1005059. https://doi.org/10.1371/journal.ppat.1005059