title: Viral disruption of promyelocytic leukemia (PML) nuclear bodies by hijacking host PML regulators.
abstract: Epstein-Barr virus (EBV) latent infection promotes cell survival and proliferation, in some cases contributing to tumourigenesis. EBV-immortalized cells and EBV-induced tumours express the viral EBNA1 protein which, in addition to its roles in replicating and maintaining EBV genomes, can alter cellular processes, including the disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) through the degradation of PML proteins. PML NBs are based on PML proteins and mediate several cellular processes including apoptosis, DNA repair and antiviral responses. Accordingly, EBNA1 expression decreases apoptosis and DNA repair which may contribute to malignant transformation. The ability of EBNA1 to disrupt PML NBs has recently been shown to require EBNA1 binding to two host proteins, the protein kinase CK2 and deubiquitylating protein USP7/HAUSP, both of which are known to be partially associated with PML NBs. EBNA1 increases the association of both CK2 and USP7 with PML NBs and, as a result, increases phosphorylation of PML proteins by CK2, a modification that is known to trigger PML polyubiquitylation and degradation. Recent data also implicates USP7 as a negative regulator of PML proteins and nuclear bodies by a mechanism independent of its intrinsic ubiquitin cleavage activity. The results suggest that EBNA1 usurps two host PML regulators in order to promote degradation of PML proteins and loss of PML NBs.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. lori.frappier@utoronto.ca
authors.forename: Lori
authors.initials: L
authors.lastname: Frappier
mesh_terms: D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000821:virology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C070576:PML protein, human; D047390:Casein Kinase II; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; C417029:EBV-encoded nuclear antigen 1