The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus

Zhilong Yang, Charles Wood

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The replication and transcription activator (RTA) protein of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human herpesvirus 8 functions as the key regulator to induce KSHV lytic replication from latency through activation of the lytic cascade of KSHV. Elucidation of the host factors involved in RTA-mediated transcriptional activation is pivotal for understanding the transition between viral latency and lytic replication. KSHV-RTA binding protein (K-RBP) was previously isolated as a cellular RTA binding protein of unknown function. Sequence analysis showed that K-RBP contains a Kruppel-associated box (KRAB) at the N terminus and 12 adjacent zinc finger motifs. In similarity to other KRAB-containing zinc finger proteins, K-RBP is a transcriptional repressor. Mutational analysis revealed that the KRAB domain is responsible for the transcriptional suppression activity of this protein and that the repression is histone deacetylase independent. K-RBP was found to repress RTA-mediated transactivation and interact with TIF1β (transcription intermediary factor 1β), a common corepressor of KRAB-containing protein, to synergize with K-RBP in repression. Overexpression and knockdown experiment results suggest that K-RBP is a suppressor of RTA-mediated KSHV reactivation. Our findings suggest that the KRAB-containing zinc finger protein K-RBP can suppress RTA-mediated transactivation and KSHV lytic replication and that KSHV utilizes this protein as a regulator to maintain a balance between latency and lytic replication.

Original languageEnglish (US)
Pages (from-to)6294-6306
Number of pages13
JournalJournal of virology
Volume81
Issue number12
DOIs
StatePublished - Jun 1 2007

Fingerprint

Human herpesvirus 8
Human Herpesvirus 8
transcriptional activation
Transcriptional Activation
binding proteins
Herpesviridae
Carrier Proteins
transcription (genetics)
zinc finger motif
Zinc Fingers
Proteins
proteins
Virus Latency
Co-Repressor Proteins
histone deacetylase
Histone Deacetylases
Sequence Analysis
Transcription Factors
sequence analysis
transcription factors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus. / Yang, Zhilong; Wood, Charles.

In: Journal of virology, Vol. 81, No. 12, 01.06.2007, p. 6294-6306.

Research output: Contribution to journalArticle

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