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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Cycle, Cell Cycle Proteins, Cell Line, Cytoplasm, Enzyme Activation, Humans, I-kappa B Kinase, I-kappa B Proteins, Mutation, NF-kappa B, Phosphorylation, Protein Binding, Protein Interaction Mapping, Protein Processing, Post-Translational, Protein Transport, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Transcriptional Activation, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques, Ubiquitination
Mol. Biol. Cell
Date: Jul. 15, 2010
Download Curated Data For This Publication
113788
Switch View:
  • Interactions 7