Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells.

BL Precious, TS Carlos, S Goodbourn, Richard Edward Randall

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

A dynamic model of STAT1 degradation by the V protein of parainfluenza virus 5 (P1V5; formerly SV5) has been proposed. In it, the V protein functions as a bipartite adaptor linking DDB1, a component of a cellular SCF-like ubiquitin E3 ligase complex, to STAT2, which in turn binds STAT1 and presents STATI to the E3 ligase complex for ubiquitination and subsequent degradation. Furthermore, it appears that loss of STATI from the complex results in decreased affinity of V for STAT2 such that STAT2 either dissociates from V or is displaced by STAT1/STAT2 complexes, facilitating the cycling of the DDB1/P1V5 V containing E3 complex for further rounds of STAT1 ubiquitination and degradation. By determining the approximate number of molecules of V, DDB 1, STATI and STAT2 present in IFN-treated 2fFGH cells, we provide additional evidence for this dynamic model of STAT 1 degradation. These results show that (i) in IFN-treated cells there is approximately 4-fold less STAT2 and 15-fold less DDB I than STATl per cell and thus DDB I and STAT2 must repeatedly acquire more STAT 1 for degradation to go to completion, and (ii) approximately 600 molecules of V protein per cell can target as many as 120,000 molecules of STAT1 for degradation in the absence of either viral or cellular protein synthesis. The importance of this mechanism in terms of the ability of the virus to dismantle the IFN-induced anti-viral state of cells is discussed. (C) 2007 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)114 - 121
Number of pages8
JournalVirology
Volume368
DOIs
Publication statusPublished - 10 Nov 2007

Keywords

  • STAT
  • interferon
  • DDB1
  • IFN-induced anti-viral state
  • PIV5
  • SV5
  • STRAND RNA VIRUSES
  • UBIQUITIN LIGASE COMPLEXES
  • PARAMYXOVIRUS-V PROTEIN
  • ALPHA/BETA-INTERFERON
  • BINDING-PROTEIN
  • DEGRADATION
  • SIMIAN-VIRUS-5
  • INDUCTION
  • REPAIR

Fingerprint

Dive into the research topics of 'Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells.'. Together they form a unique fingerprint.

Cite this