CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.
Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.
Pubmed ID: 10962033
- Leonardi A
- Chariot A
- Claudio E
- Cunningham K
- Siebenlist U
Proceedings of the National Academy of Sciences of the United States of America
September 12, 2000
- Adaptor Proteins, Signal Transducing
- Amino Acid Sequence
- Carrier Proteins
- Cell Line
- DNA, Complementary
- Enzyme Activation
- I-kappa B Kinase
- JNK Mitogen-Activated Protein Kinases
- Mitogen-Activated Protein Kinases
- Molecular Sequence Data
- Protein Binding
- Protein-Serine-Threonine Kinases
- Signal Transduction
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
- Candidiasis, familial, 8 is related to genes TRAF3IP2, C6orf5, ACT1, CIKS, C6orf4, C6orf6, PSORS13, CANDF8 which are autosomal recessive according to the OMIM database.
- Psoriasis susceptibility 13 is related to genes TRAF3IP2, C6orf5, ACT1, CIKS, C6orf4, C6orf6, PSORS13, CANDF8.