title: Analysis of the SUMO2 Proteome during HSV-1 Infection.
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.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, The Sir Michael Stoker Building, University of Glasgow Garscube Campus, Glasgow, Scotland, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sloan
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, United Kingdom.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tatham
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, The Sir Michael Stoker Building, University of Glasgow Garscube Campus, Glasgow, Scotland, United Kingdom.
authors.forename: Marine
authors.initials: M
authors.lastname: Groslambert
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, The Sir Michael Stoker Building, University of Glasgow Garscube Campus, Glasgow, Scotland, United Kingdom.
authors.forename: Mandy
authors.initials: M
authors.lastname: Glass
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, The Sir Michael Stoker Building, University of Glasgow Garscube Campus, Glasgow, Scotland, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Orr
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, United Kingdom.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, The Sir Michael Stoker Building, University of Glasgow Garscube Campus, Glasgow, Scotland, United Kingdom.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Everett
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D018259:Herpesvirus 1, Human; D054884:Host-Pathogen Interactions; D006801:Humans; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D020543:Proteome; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins