The Scaffold Protein TANK/I-TRAF Inhibits NF-κB Activation by Recruiting Polo-like Kinase 1

TANK/I-TRAF is a TRAF-binding protein that negatively regulates NF-kappa B 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-kappa B transcriptional activation induced by TNF-alpha, IL-1 beta, or several activators, but not by nuclear transcription factor p65. PLK1 expression reduces the DNA-binding activity of NF-kappa B induced by TNF-alpha. Moreover, endogenous activation of PLK1 reduces the TNF-induced phosphorylation of endogenous I kappa B alpha. PLK1 is bound to NEMO (IKK gamma) 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-kappa B activation and provide direct evidence that PLK1 is required for the repression function of TANK.