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.
Zhang
Wanqiao
W
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Wang
Jian
J
Zhang
Ying
Y
Yuan
Yanzhi
Y
Guan
Wei
W
Jin
Chaozhi
C
Chen
Hui
H
Wang
Xiaohui
X
Yang
Xiaoming
X
He
Fuchu
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination / Q000187:drug effects; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D000097869:Polo-Like Kinase 1; C491731:IKBKG protein, human; C000606204:NFKBIA protein, human; C484406:TANK protein, human; C403191:TBK1 protein, human