The scaffold protein TANK/I-TRAF inhibits NF-kappaB activation by recruiting polo-like kinase 1

Mol Biol Cell. 2010 Jul 15;21(14):2500-13. doi: 10.1091/mbc.e09-08-0715. Epub 2010 May 19.

Abstract

TANK/I-TRAF is a TRAF-binding protein that negatively regulates NF-kappaB activation. The underlying mechanism of this activity remains unclear. Here we show that TANK directly interacts with PLK1, a conserved cell cycle-regulated kinase. PLK1 inhibits NF-kappaB transcriptional activation induced by TNF-alpha, IL-1beta, or several activators, but not by nuclear transcription factor p65. PLK1 expression reduces the DNA-binding activity of NF-kappaB induced by TNF-alpha. Moreover, endogenous activation of PLK1 reduces the TNF-induced phosphorylation of endogenous IkappaBalpha. PLK1 is bound to NEMO (IKKgamma) through TANK to form a ternary complex in vivo. We describe a new regulatory mechanism for PLK1: PLK1 negatively regulates TNF-induced IKK activation by inhibiting the ubiquitination of NEMO. These findings reveal that the scaffold protein TANK recruits PLK1 to negatively regulate NF-kappaB activation and provide direct evidence that PLK1 is required for the repression function of TANK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cytoplasm / drug effects
  • Cytoplasm / enzymology
  • Enzyme Activation / drug effects
  • Humans
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / metabolism
  • Mutation / genetics
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Polo-Like Kinase 1
  • Protein Binding / drug effects
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational / drug effects
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Two-Hybrid System Techniques
  • Ubiquitination / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • I-kappa B Proteins
  • IKBKG protein, human
  • NF-kappa B
  • NFKBIA protein, human
  • Proto-Oncogene Proteins
  • TANK protein, human
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase