title: Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is the likely infectious cause of Kaposi's sarcoma, primary effusion lymphoma, and some cases of multicentric Castleman's disease. Its latent nuclear antigen (LANA) is expressed in the nuclei of latently infected cells and may play a role in the persistence of episomal viral DNA in dividing cells. Here we report that LANA interacts with RING3, a nuclear protein and member of the Drosophila fsh (female sterile homeotic) family of proteins, some of which have previously been implicated in controlling gene expression. Binding of RING3 to LANA involves the ET domain, characteristic of fsh-related proteins, suggesting that this highly conserved region is involved in protein-protein interactions. The interaction between RING3 and LANA results in phosphorylation of serine and threonine residues located between amino acids 951 and 1107 in the carboxy-terminal region of LANA. However, RING3 is not itself a kinase but appears to recruit an as yet unidentified serine/threonine protein kinase into the complex which it forms with LANA.
authors.affiliation: Molecular Virology Group, Department of Medical Microbiology and Genitourinary Medicine, The University of Liverpool, Liverpool L69 3GA, United Kingdom.
authors.forename: G M
authors.initials: GM
authors.lastname: Platt
authors.forename: G R
authors.initials: GR
authors.lastname: Simpson
authors.forename: S
authors.initials: S
authors.lastname: Mittnacht
authors.forename: T F
authors.initials: TF
authors.lastname: Schulz
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D004330:Drosophila / Q000235:genetics; D005260:Female; D017344:Genes, Insect; D019288:Herpesvirus 8, Human; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000092468:Bromodomain Containing Proteins
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C118485:latent nuclear antigen (LNA)