title: K-bZIP of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) binds KSHV/HHV-8 Rta and represses Rta-mediated transactivation.
abstract: The regulatory circuit for Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) gene expression bears resemblance to that of Epstein-Barr virus (EBV), but with interesting differences. Based on protein sequence similarities and synteny to their EBV counterparts, two KSHV/HHV-8 viral regulatory factors, HHV-8 Rta and K-bZIP, encoded by open reading frame (ORF) 50 and ORF K8, respectively, have been identified. Rta is an immediate early transcriptional activator that activates lytic viral replication and mediates viral reactivation from latency, while ORF K8 is an early gene activated by Rta. Extensive splicing of ORF K8 mRNA leads to the production of K-bZIP, a protein of the basic domain-leucine zipper (bZIP) family. The role of K-bZIP in viral replication, however, remains unresolved. Here, we report that K-bZIP is a nuclear protein that binds Rta directly both in vivo and in vitro and represses Rta-mediated transactivation of the K-bZIP promoter. We further demonstrate that the leucine zipper domain of K-bZIP is required for Rta binding and a K-bZIP mutant lacking the leucine zipper does not repress Rta activity. Finally, the K-bZIP-mediated repression of Rta transactivation cannot be restored by overexpression of the transcriptional coactivator p300 or the p300-CBP-associated factor, P/CAF. Our results suggest that K-bZIP is involved in a feedback circuit to turn off its own expression and possibly the expression of other early genes activated by Rta.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Su-Fan
authors.initials: SF
authors.lastname: Lin
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Chou-Zen
authors.initials: CZ
authors.lastname: Giam
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D016350:Leucine Zippers; D011485:Protein Binding; D012097:Repressor Proteins; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000378:metabolism*; D014775:Virus Activation
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D017874:Immediate-Early Proteins; C118265:K8 protein, Human herpesvirus 8; D012097:Repressor Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins