Anti-IKKα Antibody

I-kappa-B kinase α, IKK-A, IKK-α, IkBKA, IkappaB kinase, EC 2.7.11.10, Conserved helix-loop-helix ubiquitous kinase, I-kappa-B kinase 1, IKK1, Nuclear factor NF-kappa-B inhibitor kinase α, NFKBIKA, Transcription factor 16, TCF-16

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 (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). 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 (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). 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 (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). 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) (PubMed:21765415). 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 (PubMed:20501937). 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 (PubMed:17434128). 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 (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {UniProtKB:Q60680, PubMed:12789342, PubMed:15084260, PubMed:17434128, PubMed:20434986, PubMed:20501937, PubMed:21765415, PubMed:30217973, PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576}.

Nuclear factor kappa B (NF-kappaB) is a ubiquitous transcription factor and key mediator of gene expression during immune and inflammatory responses. NF-kappaB activates numerous genes in response to extracellular stimuli, such as IL-1, TNFalpha, and LPS. NF-kappaB is associated with IkappaB in cytoplasm, which inhibits NF-kappaB activity. IkappaB kinase (IKK), which phosphorylates IkappaB and mediates IkappaB degradation and NF-kappaB activation, was recently identified. IKK is a serine protein kinase, and the IKK complex contains alpha and beta subunits (IKKalpha and IKKbeta). IKKalpha and IKKbeta interact with each other, and both are essential for NF-B activation. IKKalpha specifically phosphorylates IkappaB-alpha and is expressed in a variety of human tissues.