Composition and assembly of STAT-targeting ubiquitin ligase complexes: Paramyxovirus V protein carboxyl terminus is an oligomerization domain

Christina M. Ulane, Alex Kentsis, Cristian D. Cruz, Jean Patrick Parisien, Kristi L. Schneider, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Transcription regulators STAT1 and STAT2 are key components of the interferon signaling system leading to innate antiviral immunity. The related STAT3 protein is a regulator of interleukin-6-type cytokine signals and can contribute to both cell growth and death important for cancer gene regulation and tumor survival. These three STAT proteins are targeted for proteasome-mediated degradation by RNA viruses in the Rubulavirus genus of the Paramyxoviridae. A single viral protein, the V protein, assembles STAT-specific ubiquitin ligase complexes from cellular components. Simian virus 5 (SV5) targets STAT1, human parainfluenza virus 2 targets STAT2, and mumps virus targets both STAT1 and STAT3. Analysis of the V-dependent degradation complex (VDC) composition and assembly revealed several features contributing to targeting specificity. SV5 and mumps V proteins require STAT2 to recruit the STAT1 target, yet mumps V protein binds STAT3 independent of STAT1 and STAT2. All Rubulavirus V proteins tested require cellular DDB1 to target STATs for degradation but differ in the use of Roc1, which is essential for mumps V STAT3 targeting. Protein interaction analysis reveals that paramyxovirus V proteins can homo- and heterooligomerize and that the conserved cysteine-rich zinc-binding C-terminal domain is necessary and sufficient for oligomerization. Purified SV5 V protein spontaneously assembles into spherical macromolecular particles, and similar particles constitute SV5 and mumps VDC preparations.

Original languageEnglish (US)
Pages (from-to)10180-10189
Number of pages10
JournalJournal of virology
Volume79
Issue number16
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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