Poly(ADP-Ribose) Polymerase 1 and Ste20-Like Kinase hKFC Act as Transcriptional Repressors for Gamma-2 Herpesvirus Lytic Replication

Yousang Gwack, Hiroyuki Nakamura, Sun Hwa Lee, John Souvlis, Jason T. Yustein, Steve Gygi, Hsing-Jien Kung, Jae U. Jung

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The replication and transcription activator (RTA) of gamma-2 herpesvirus is sufficient to drive the entire virus lytic cycle. Hence, the control of RTA activity should play an important role in the maintenance of viral latency. Here, we demonstrate that cellular poly(ADP-ribose) polymerase 1 (PARP-1) and Ste20-like kinase hKFC interact with the serine/threonine-rich region of gamma-2 herpesvirus RTA and that these interactions efficiently transfer poly(ADP-ribose) and phosphate units to RTA. Consequently, these modifications strongly repressed RTA-mediated transcriptional activation by inhibiting its recruitment onto the promoters of virus lytic genes. Conversely, the genetic ablation of PARP-1 and hKFC interaction or the knockout of the PARP-1 gene and activity considerably enhanced gamma-2 herpesvirus lytic replication. Thus, this is the first demonstration that cellular PARP-1 and hKFC act as molecular sensors to regulate RTA activity and thereby, herpesvirus latency.

Original languageEnglish (US)
Pages (from-to)8282-8294
Number of pages13
JournalMolecular and Cellular Biology
Volume23
Issue number22
DOIs
StatePublished - Nov 2003

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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