CHUK protein, Human (Active, sf9, His, GST)

CHUK is a serine kinase that plays a pivotal role in the NF-kappa-B signaling pathway, which is activated by various stimuli including inflammatory cytokines, bacterial or viral products, and DNA damage. As part of the canonical IKK complex, CHUK phosphorylates NF-kappa-B inhibitors on serine residues, leading to their ubiquitination and subsequent proteasomal degradation, thereby releasing NF-kappa-B to translocate into the nucleus and activate the transcription of hundreds of genes involved in immune response, growth control, or anti-apoptosis. Additionally, CHUK negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 to promote the assembly of the A20/TNFAIP3 ubiquitin-editing complex, limiting inflammatory gene activation. In the non-canonical NF-kappa-B pathway, 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 that regulate B-cell survival and lymphoid organogenesis. CHUK also participates in the negative feedback of this pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, CHUK phosphorylates CREBBP to enhance its transcriptional and histone acetyltransferase activities, and modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histone H3 at Ser-10, which is subsequently acetylated at Lys-14 by CREBBP. Furthermore, CHUK phosphorylates the CREBBP-interacting protein NCOA3 and the pro-apoptotic transcription factor FOXO3. By similarity, CHUK phosphorylates RIPK1 at Ser-25 to repress its kinase activity, preventing TNF-mediated RIPK1-dependent cell death. Following mitophagy induction, CHUK phosphorylates AMBRA1 to promote its interaction with ATG8 family proteins and enhance its mitophagic activity.