Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components

Christina M. Ulane, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

Signal transducer and activator of transcription (STAT) proteins are normally long-lived, but infection with certain Paramyxoviruses results in efficient loss of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called "V" is sufficient to mediate the destruction of STAT proteins. STAT degradation is blocked by proteasome inhibitors, strongly implicating the ubiquitin (Ub)-proteasome targeting system. We demonstrate that cellular expression of V proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2) induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins catalyze Ub transfer in an ATP-dependent process that requires both Ub-activating (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting protein partners were isolated by affinity purification from human cells and reveal a complex of associated cellular proteins. This complex includes both STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a protein related to a family of cellular Ub ligase complex subunits, cullin 4A (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in STAT1 degradation by SV5 infection were analyzed using small interfering RNAs. These findings demonstrate the assembly of a V-dependent degradation complex that includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on SCF-type cellular E3 enzymes, we refer to this complex as VDC.

Original languageEnglish (US)
Pages (from-to)160-166
Number of pages7
JournalVirology
Volume304
Issue number2
DOIs
StatePublished - Jan 1 2002

Keywords

  • Cullin 4A
  • DDB1
  • Interferon
  • Paramyxovirus
  • STAT1
  • STAT2
  • SV5, HPIV2
  • V protein

ASJC Scopus subject areas

  • Virology

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