Expanding CYLD protein in NF-κβ/TNF-α signaling pathway in response to Lactobacillus acidophilus in non-metastatic rectal cancer patients

A schematic plot of probiotic consumption Effects on the CYLD protein in regulating the NF-ĸβ signaling pathway in colorectal cancer. NF-ĸβ can be activated by canonical and noncanonical pathways, which rely on IκB degradation and p100 processing, respectively. In the canonical NF-κβ pathway, dimmers, such as p65/p50, are maintained in the cytoplasm by interacting with an IκBα protein. The binding of a ligand to a cell-surface receptor activates TRAF2, which triggers an IKK complex, containing -α, -β, -g, which phosphorylates IKK-β. It then phosphorylates IκB-α, leading to K48-ubiquitination and degradation of this protein. The p65/p50 protein freely enters the nucleus to turn on target genes. The non-canonical pathway is primarily involved in p100/RelB activation. It differs from the classical pathway in that only certain receptor signals activate this pathway. It proceeds through an IKK complex that contains two IKK-α subunits but not NEMO. Several materials including peptidoglycan, phorbol, myristate, acetate, and gram-positive bacteria such as probiotics inhibit NF-κB by inducing CYLD. This protein can block the canonical and noncanonical NF-κβ pathways by removing Lys-63 ubiquitinated chains from activated TRAFs, RIP, NEMO, and IKK (α, β, and γ). Moreover, TNF-α induces apoptosis by binding caspase-3 to FADD.