title: Kaposi's sarcoma-associated herpesvirus (KSHV) Rta and cellular HMGB1 proteins synergistically transactivate the KSHV ORF50 promoter.
abstract: Kaposi's sarcoma-associated herpesvirus 'replication transcriptional activator' (Rta) plays a critical role in the switch from latency to lytic replication. Rta upregulates several lytic KSHV genes, including its own, through multiple mechanisms. We demonstrate that cellular HMGB1 binds and synergistically upregulates the ORF50 promoter in conjunction with Rta. No direct interaction between Rta and HMGB1 was observed, however a ternary complex is formed in the presence of Oct1. Furthermore, deletion of an Oct-1 binding site within the ORF50 promoter ablates the HMGB1-mediated synergistic response. These results suggest Rta autostimulation may be mediated by a transient complex involving Oct1 and HMGB1.
authors.affiliation: Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Harrison
authors.forename: Adrian
authors.initials: A
authors.lastname: Whitehouse
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D024243:HMGB1 Protein / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D016366:Open Reading Frames; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; D024243:HMGB1 Protein; D017874:Immediate-Early Proteins; D027702:Organic Cation Transporter 1; D015534:Trans-Activators