Role of the adaptor protein CIKS in the activation of the IKK complex.
Nuclear factor kappaB (NF-kappaB) plays a pivotal role in numerous cellular processes, including stress response, inflammation, and protection from apoptosis. Therefore, the activity of NF-kappaB needs to be tightly regulated. We have previously identified a novel gene, named CIKS (connection to IkappaB-kinase and SAPK), able to bind the regulatory sub-unit NEMO/IKKgamma and to activate NF-kappaB. Here, we demonstrate that CIKS forms homo-oligomers, interacts with NEMO/IKKgamma, and is recruited to the IKK-complex upon cell stimulation. In addition, we identified the regions of CIKS responsible for these functions. We found that the ability of CIKS to oligomerize, and to be recruited to the IKK-complex is not sufficient to activate the NF-kappaB. In fact, a deletion mutant of CIKS able to oligomerize, to interact with NEMO/IKKgamma, and to be recruited to the IKK-complex does not activate NF-kappaB, suggesting that CIKS needs a second level of regulation to efficiently activate NF-kappaB.
Mauro
Claudio
C
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, Italy.
Vito
Pasquale
P
Mellone
Stefano
S
Pacifico
Francesco
F
Chariot
Alain
A
Formisano
Silvestro
S
Leonardi
Antonio
A
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D015153:Blotting, Western; D019013:CD40 Antigens / Q000096:biosynthesis; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002845:Chromatography; D002850:Chromatography, Gel; D019281:Dimerization; D004789:Enzyme Activation; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D007249:Inflammation; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
D048868:Adaptor Proteins, Signal Transducing; D019013:CD40 Antigens; D002352:Carrier Proteins; D016328:NF-kappa B; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human