Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta

Physical association and promoter-dependent transcriptional repression

Yoshihiro Izumiya, Su Fang Lin, Thomas Ellison, Ling Yu Chen, Chie Izumiya, Paul Luciw, Hsing Jien Kung

Research output: Contribution to journalArticle

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Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma and B-cell neoplasms. The genomic organization of KSHV is similar to that of Epstein-Barr virus (EBV). EBV encodes two transcriptional factors, Rta and Zta, which functionally interact to transactivate EBV genes during replication and reactivation from latency. KSHV encodes a basic leucine zipper protein (K-bZIP), a homologue of EBV Zta, and K-Rta, the homologue of EBV Rta. EBV Rta and Zta are strong transcriptional transactivators. Although there is ample evidence that K-Rta is a potent transactivator, the role of K-bZIP as a transcriptional factor is much less clear. In this study, we report that K-bZIP modulates K-Rta function. We show that K-bZIP directly interacts with K-Rta in vivo and in vitro. This association is specific, requiring the basic domain (amino acids 122 to 189) of K-bZIP and a specific region (amino acids 499 to 550) of K-Rta, and can be detected with K-bZIP and K-Rta endogenously expressed in BCBL-1 cells treated with tetradecanoyl phorbol acetate. The functional relevance of this association was revealed by the observation that K-bZIP represses the transactivation of the ORF57 promoter by K-Rta in a dose-dependent manner. K-bZIP lacking the interaction domain fails to repress K-Rta-mediated transactivation; this finding attests to the specificity of the repression. Interestingly, this repression is not observed for the promoter of polyadenylated nuclear (PAN) RNA, another target of K-Rta; thus, repression is promoter dependent. Finally, we provide evidence that the modulation of K-Rta by K-bZIP also occurs in vivo during reactivation of the viral genome in BCBL-1 cells. When K-bZIP is overexpressed in BCBL-1 cells, the level of expression of ORF57 but not PAN RNA is repressed. These data support the model that one function of K-bZIP is to modulate the activity of the transcriptional transactivator K-Rta.

Original languageEnglish
Pages (from-to)1441-1451
Number of pages11
JournalJournal of Virology
Volume77
Issue number2
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

Fingerprint

Human herpesvirus 8
Human herpesvirus 4
Human Herpesvirus 8
Human Herpesvirus 4
promoter regions
Trans-Activators
Nuclear RNA
transcriptional activation
Transcriptional Activation
transcription factors
RNA
Leucine Zippers
Basic Amino Acids
leucine zipper
Messenger RNA
amino acids
Kaposi's Sarcoma
Viral Genome
sarcoma
cells

ASJC Scopus subject areas

  • Immunology

Cite this

Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta : Physical association and promoter-dependent transcriptional repression. / Izumiya, Yoshihiro; Lin, Su Fang; Ellison, Thomas; Chen, Ling Yu; Izumiya, Chie; Luciw, Paul; Kung, Hsing Jien.

In: Journal of Virology, Vol. 77, No. 2, 01.01.2003, p. 1441-1451.

Research output: Contribution to journalArticle

Izumiya, Yoshihiro ; Lin, Su Fang ; Ellison, Thomas ; Chen, Ling Yu ; Izumiya, Chie ; Luciw, Paul ; Kung, Hsing Jien. / Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta : Physical association and promoter-dependent transcriptional repression. In: Journal of Virology. 2003 ; Vol. 77, No. 2. pp. 1441-1451.
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abstract = "Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma and B-cell neoplasms. The genomic organization of KSHV is similar to that of Epstein-Barr virus (EBV). EBV encodes two transcriptional factors, Rta and Zta, which functionally interact to transactivate EBV genes during replication and reactivation from latency. KSHV encodes a basic leucine zipper protein (K-bZIP), a homologue of EBV Zta, and K-Rta, the homologue of EBV Rta. EBV Rta and Zta are strong transcriptional transactivators. Although there is ample evidence that K-Rta is a potent transactivator, the role of K-bZIP as a transcriptional factor is much less clear. In this study, we report that K-bZIP modulates K-Rta function. We show that K-bZIP directly interacts with K-Rta in vivo and in vitro. This association is specific, requiring the basic domain (amino acids 122 to 189) of K-bZIP and a specific region (amino acids 499 to 550) of K-Rta, and can be detected with K-bZIP and K-Rta endogenously expressed in BCBL-1 cells treated with tetradecanoyl phorbol acetate. The functional relevance of this association was revealed by the observation that K-bZIP represses the transactivation of the ORF57 promoter by K-Rta in a dose-dependent manner. K-bZIP lacking the interaction domain fails to repress K-Rta-mediated transactivation; this finding attests to the specificity of the repression. Interestingly, this repression is not observed for the promoter of polyadenylated nuclear (PAN) RNA, another target of K-Rta; thus, repression is promoter dependent. Finally, we provide evidence that the modulation of K-Rta by K-bZIP also occurs in vivo during reactivation of the viral genome in BCBL-1 cells. When K-bZIP is overexpressed in BCBL-1 cells, the level of expression of ORF57 but not PAN RNA is repressed. These data support the model that one function of K-bZIP is to modulate the activity of the transcriptional transactivator K-Rta.",
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