title: Kaposi's sarcoma-associated herpesvirus-encoded protein kinase and its interaction with K-bZIP.
abstract: The oncogenic herpesvirus, Kaposi's sarcoma-associated herpesvirus, also identified as human herpesvirus 8, contains genes producing proteins that control transcription and influence cell signaling. Open reading frame 36 (ORF36) of this virus encodes a serine/threonine protein kinase, which is designated the viral protein kinase (vPK). Our recent efforts to elucidate the role of vPK in the viral life cycle have focused on identifying viral protein substrates and determining the effects of vPK-mediated phosphorylation on specific steps in viral replication. The vPK gene was transcribed into 4.2-kb and 3.6-kb mRNAs during the early and late phases of viral reactivation. vPK is colocalized with viral DNA replication/transcription compartments as marked by a polymerase processivity factor, and K-bZIP, a protein known to bind the viral DNA replication origin (Ori-Lyt) and to regulate viral transcription. The vPK physically associated with and strongly phosphorylated K-bZIP at threonine 111, a site also recognized by the cyclin-dependent kinase Cdk2. Both K-bZIP and vPK were corecruited to viral promoters targeted by K-bZIP as well as to the Ori-Lyt region. Phosphorylation of K-bZIP by vPK had a negative impact on K-bZIP transcription repression activity. The extent of posttranslational modification of K-bZIP by sumoylation, a process that influences its repression function, was decreased by vPK phosphorylation at threonine 111. Our data thus identify a new role of vPK as a modulator of viral transcription.
authors.affiliation: University of California-Davis, Cancer Center, Research III Room 2400B, 4645 2nd Ave., Sacramento, CA 95817, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Chie
authors.initials: C
authors.lastname: Izumiya
authors.forename: Albert
authors.initials: A
authors.lastname: Van Geelen
authors.forename: Don-Hong
authors.initials: DH
authors.lastname: Wang
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Paul A
authors.initials: PA
authors.lastname: Luciw
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C118265:K8 protein, Human herpesvirus 8; D012097:Repressor Proteins; D014764:Viral Proteins; D011494:Protein Kinases