nf 25

CYP3A4 is an important member of the cytochrome P450 enzyme superfamily, with 33 allelic variants. Human cytochrome P450 3A4 (CYP3A4) is an important drug metabolizing enzyme involved in a number of drug-drug and food-drug interactions. Systemic inflammation has been linked to suppressed CYP3A4 activity.

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. Phosphorylates inhibitors of NF-kappa-B on 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus.

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. Phosphorylates inhibitors of NF-kappa-B on 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus.

Interleukin 25 (IL-25) belongs to the Interleukin 17 (IL-17) family of proteins, which is comprised of six members (IL-17, IL-17B through IL-17F). These proteins are secreted and are structurally related by sharing a conserved cysteine-knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus. With the exception of IL-17B, which exists as a non-covalently linked dimer, all IL-17 family members are disulfide-linked dimers. IL-17 family proteins are pro-inflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions. Human interleukin-17E (IL17E), also referred to as Interleukin-25 (IL25), is a distinct member of the IL17 cytokine family comprised of at least six members sharing a conserved cysteine-knot structure but divergent at the N-terminus. IL25 is a glycoprotein secreted as dimers by innate effector eosinophils and basophils, and present at very low levels in various peripheral tissues. IL25, together with IL17B, are ligands for the cytokine receptor IL17BR, and the cross-linking induces NF-κB activation and production of the proinflammatory chemokine IL-8, as well as ERK, JNK, and p38 activation. Overexpression of IL25 gene in transgenic mice suggested that this cytokine can regulate hematopoietic and immune functions, and additionally is identified as a proinflammatory cytokine favoring Th2-type immune responses possibly by enhancing the maintenance and functions of adaptive Th2 memory cells.