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

研究成果: 雜誌貢獻文章同行評審

67 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)8282-8294
頁數13
期刊Molecular and Cellular Biology
23
發行號22
DOIs
出版狀態已發佈 - 11月 1 2003
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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