CHUK
CHUK (component of inhibitor of nuclear factor kappa B kinase complex, also known as IKK1, IKK-alpha, IKKA, IkBKA, NFKBIKA and TCF16) is a serine kinase central to NF-kappa-B signalling. It phosphorylates inhibitors of NF-kappa-B and other substrates to control gene transcription. Browse Assay Genie's current range of CHUK research reagents below, or read on for the biology behind the target.
CHUK is a serine kinase with an essential role in the NF-kappa-B signalling pathway, which is activated by inflammatory cytokines, bacterial or viral products, DNA damage and other cellular stresses. As part of the canonical IKK complex, it phosphorylates inhibitors of NF-kappa-B on serine residues. This allows their polyubiquitination and degradation by the proteasome, so free NF-kappa-B moves into the nucleus and activates transcription of hundreds of genes involved in immune response, growth control and protection against apoptosis.
CHUK also acts as a brake on the pathway. By phosphorylating the scaffold protein TAXBP1, it promotes assembly of the A20/TNFAIP3 ubiquitin-editing complex (A20/TNFAIP3, TAX1BP1 and the E3 ligases ITCH and RNF11), limiting inflammatory gene activation. In the non-canonical pathway, the MAP3K14-activated CHUK homodimer phosphorylates NFKB2/p100 bound to RelB, driving processing to p52 and formation of RelB-p52 complexes that regulate genes for B-cell survival and lymphoid organogenesis. It further provides negative feedback by phosphorylating and destabilising MAP3K14/NIK.
Within the nucleus, CHUK phosphorylates CREBBP, increasing its transcriptional and histone acetyltransferase activities, and phosphorylates histone H3 at Ser-10, which is then acetylated at Lys-14 by CREBBP. Other substrates include NCOA3, FOXO3, RIPK1 (Ser-25, which represses its kinase activity and prevents TNF-mediated RIPK1-dependent cell death) and AMBRA1 following mitophagy induction. The CHUK gene encodes a member of the I-kappa-B kinase subfamily of the Ser/Thr protein kinase family; its previous name was conserved helix-loop-helix ubiquitous kinase, and the mouse ortholog is Chuk.
CHUK phosphorylates NF-kappa-B inhibitors, triggering their degradation and enabling transcription of genes for immune response, growth control and protection against apoptosis.
Phosphorylation of TAXBP1 promotes assembly of the A20 ubiquitin-editing complex, making CHUK a key node in negative feedback of inflammatory gene activation.
In the non-canonical pathway, CHUK drives NFKB2 p100 processing to p52, regulating genes involved in B-cell survival and lymphoid organogenesis.
CHUK phosphorylates RIPK1 to prevent TNF-mediated cell death and phosphorylates AMBRA1 after mitophagy induction, linking it to survival and mitochondrial quality control.
CHUK is a serine kinase in the canonical IKK complex. It phosphorylates inhibitors of NF-kappa-B, leading to their proteasomal degradation and NF-kappa-B activation. It also drives non-canonical signalling by processing NFKB2/p100 to p52, and phosphorylates nuclear substrates such as CREBBP and histone H3.
CHUK is also called IKK1, IKK-alpha, IKKA, IkBKA, NFKBIKA and TCF16. Its UniProt name is inhibitor of nuclear factor kappa-B kinase subunit alpha, and its former HGNC name was conserved helix-loop-helix ubiquitous kinase. It belongs to the I kappa B kinase family and the IKK complex gene group.
The mouse ortholog is Chuk. The protein belongs to the protein kinase superfamily, I-kappa-B kinase subfamily. It regulates NF-kappa-B signalling, which controls genes for immune response, growth control and apoptosis protection, and also limits inflammatory signalling through negative feedback. Check the datasheet of any product for its validated reactivity.
Other NF-kappa-B pathway kinases, substrates, feedback regulators and cell death and mitophagy proteins linked to CHUK.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O15111; product specifications from Assay Genie datasheets.