Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1

B Precious, K Childs, V Fitzpatrick-Swallow, S Goodbourn, Richard Edward Randall

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

The V protein of simian virus 5 (SV5) facilitates the ubiquitination and subsequent proteasome-mediated degradation of STAT1. Here we show, by visualizing direct protein-protein interactions and by using the yeast two-hybrid system, that while the SV5 V protein fails to bind to STAT1 directly, it binds directly and independently to both DDB1 and STAT2, two cellular proteins known to be essential for SV5-mediated degradation of STAT1. We also demonstrate that STATI and STAT2 interact independently of SV5 V and show that SV5 V protein acts as an adaptor molecule linking DDB1 to STAT2/STAT1 heterodimers, which in the presence of additional accessory cellular proteins, including Cullin 4a, can ubiquitinate STATI. Additionally, we show that the avidity of STAT2 for V is relatively weak but is significantly enhanced by the presence of both STAT1 and DDB1, i.e., the complex of STAT1, STAT2, DDB1, and SV5 V is more stable than a complex of STAT2 and V. From these studies we propose a dynamic model in which SV5 V acts as a bridge, bringing together a DDB1/Cullin 4a-containing ubiquitin ligase complex and STAT1/STAT2 heterodimers, which leads to the degradation of STATI. The loss of STAT1 results in a decrease in affinity of binding of STAT2 for V such that STAT2 either dissociates from V or is displaced from V by STAT1/STAT2 complexes, thereby ensuring the cycling of the DDB1 and SV5 V containing E3 complex for continued rounds of STATI ubiquitination and degradation.

Original languageEnglish
Pages (from-to)13434-13441
Number of pages8
JournalJournal of Virology
Volume79
Issue number21
DOIs
Publication statusPublished - Nov 2005

Keywords

  • PARAINFLUENZA VIRUS TYPE-2
  • DNA-BINDING PROTEIN
  • ALPHA/BETA-INTERFERON
  • IN-VITRO
  • DEGRADATION
  • LIGASE
  • DAMAGE
  • DOMAIN
  • REPLICATION
  • ACTIVATION

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