State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Mol Biol Cell. 2010 Jul 15;21(14):2500-13. doi: 10.1091/mbc.e09-08-0715. Epub 2010 May 19.
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.
TANK/I-TRAF 是一种 TRAF 结合蛋白，可负向调节 NF-κB 的激活。其活性的潜在机制尚不清楚。本文中，我们发现 TANK 可直接与 PLK1（一种保守的细胞周期调节激酶）相互作用。PLK1 可抑制 TNF-α、IL-1β或几种激活剂诱导的 NF-κB 转录激活，但不抑制核转录因子 p65。PLK1 表达可降低 TNF-α诱导的 NF-κB 的 DNA 结合活性。此外，内源性 PLK1 的激活可降低 TNF 诱导的内源性 IkappaBalpha 的磷酸化。PLK1 通过 TANK 与 NEMO（IKKγ）结合形成三元复合物。我们描述了 PLK1 的一种新的调节机制：PLK1 通过抑制 NEMO 的泛素化，负向调节 TNF 诱导的 IKK 激活。这些发现表明支架蛋白 TANK 招募 PLK1 以负向调节 NF-κB 的激活，并提供了直接证据表明 PLK1 是 TANK 的抑制功能所必需的。
