Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling

J Biochem. 2009 Dec;146(6):821-32. doi: 10.1093/jb/mvp127. Epub 2009 Aug 12.


Upon activation, NF-kappaB translocates into the nucleus and initiates biological events. This NF-kappaB signalling is mainly regulated by the protein kinase IKKbeta. Early in this signalling pathway, IKKbeta is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of HTLV-1. In cells infected by HTLV-1, IKKbeta is persistently phosphorylated and conjugated with monoubiquitin due to Tax expression. Although this Tax-induced monoubiquitination appears to be an important regulation system for IKKbeta, how the monoubiquitination occurs is unknown and its role in NF-kappaB signalling is still unclear. Here, we show that an E3-ubiquitin ligase Ro52 interacts weakly with wild-type IKKbeta but strongly with a phosphomimetic mutant IKKbeta to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKbeta causes an interaction with Ro52 for the subsequent monoubiquitination. NF-kappaB reporter assays have shown that the IKKbeta activity is suppressed by wild-type Ro52, but not by its inactive mutant. In addition, monoubiquitin fusion of IKKbeta reduced its activity for NF-kappaB signalling. We also found that Ro52 dramatically reduces the level of Tax. These results suggest that Ro52 down-regulates Tax-induced NF-kappaB signalling by monoubiquitinating IKKbeta and by reducing the level of Tax.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Down-Regulation*
  • Humans
  • I-kappa B Kinase / metabolism*
  • NF-kappa B / metabolism*
  • Ribonucleoproteins / metabolism*
  • Signal Transduction / physiology*
  • Ubiquitination*


  • NF-kappa B
  • Ribonucleoproteins
  • SS-A antigen
  • I-kappa B Kinase