Key Role of Ubc5 and Lysine-63 Polyubiquitination in Viral Activation of IRF3

Wenwen Zeng, Ming Xu, Siqi Liu, Lijun Sun, Zhijian J. Chen

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


The mitochondrial antiviral signaling protein (MAVS; also known as IPS-1, VISA, and CARDIF) is essential for innate immune response against RNA viruses. MAVS transduces signals from the cytosolic RIG-I-like receptors, which bind to viral RNAs. But how MAVS activates downstream transcription factors such as IRF3 to induce type-I interferons is not well understood. We have established a cell-free system in which mitochondria derived from virus-infected cells activate IRF3 in the cytosol. Fractionation of the cytosol led to the identification of Ubc5 as a ubiquitin-conjugating enzyme (E2) required for IRF3 activation. Using an inducible RNAi strategy, we demonstrate that catalytically active Ubc5 is required for IRF3 activation by viral infection. The activation of IRF3 also requires two ubiquitin-binding domains of NEMO. Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation.

Original languageEnglish (US)
Pages (from-to)315-325
Number of pages11
JournalMolecular cell
Issue number2
StatePublished - Oct 23 2009



ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Key Role of Ubc5 and Lysine-63 Polyubiquitination in Viral Activation of IRF3'. Together they form a unique fingerprint.

Cite this