The Itch ubiquitin ligase is required for KSHV RTA induced vFLIP degradation

Jennifer C. Chmura, Kevin Herold, Ayana Ruffin, Trudymae Atuobi, Yetunde Fabiyi, Ashley E. Mitchell, Young Choi, Elana S. Ehrlich

Research output: Contribution to journalArticle

Abstract

Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA. Itch potently ubiquitinated vFLIP in vivo and in vitro. We provide evidence for interaction between RTA, vFLIP and Itch and we identified an RTA resistant mutant of vFLIP that is unable to interact with Itch. These observations contribute to our understanding of how RTA counteracts the activities of vFLIP.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalVirology
Volume501
DOIs
StatePublished - Jan 15 2017

Keywords

  • AIP4
  • Herpesvirus
  • HHV-8
  • Itch
  • Kaposi's sarcoma
  • KSHV
  • NF-κB
  • RTA
  • Ubiquitin
  • vFLIP

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Chmura, J. C., Herold, K., Ruffin, A., Atuobi, T., Fabiyi, Y., Mitchell, A. E., Choi, Y., & Ehrlich, E. S. (2017). The Itch ubiquitin ligase is required for KSHV RTA induced vFLIP degradation. Virology, 501, 119-126. https://doi.org/10.1016/j.virol.2016.11.016