|Other Names||Inhibitor of nuclear factor kappa-B kinase subunit alpha, I-kappa-B kinase alpha, IKK-A, IKK-alpha, IkBKA, IkappaB kinase, Conserved helix-loop-helix ubiquitous kinase, I-kappa-B kinase 1, IKK1, Nuclear factor NF-kappa-B inhibitor kinase alpha, NFKBIKA, Transcription factor 16, TCF-16, CHUK, IKKA, TCF16|
|Target/Specificity||The synthetic peptide sequence used to generate the antibody AP7123a was selected from the Center region of human CHUK. A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.|
|Format||The synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml deionized water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa- B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260).|
|Cellular Location||Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus|
|Tissue Location||Widely expressed.|
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Provided below are standard protocols that you may find useful for product applications.
CHUK is a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor.
Park, K.J., et al., Mol. Cell 18(1):71-82 (2005).Qing, G., et al., J. Biol. Chem. 280(11):9765-9768 (2005).Xiao, G., et al., J. Biol. Chem. 279(29):30099-30105 (2004).Gu, L., et al., J. Biol. Chem. 279(50):52141-52149 (2004).Buss, H., et al., J. Biol. Chem. 279(53):55633-55643 (2004).
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