The classical nuclear factor κB (NF-κB) signalling pathway activated by the tumour necrosis factor receptor (TNFR).
The p50 and p65 isoforms of the nuclear factor κB (NF-κB)/Rel family form the NF-κB dimer that is activated in the tumour necrosis factor α (TNFα) signalling pathway. The activated TNF receptor (TNFR) recruits a signalling complex to the membrane (Step 2), which contains the inhibitor of NF-κB (IκB) kinase (IKK) α/IKKβ dimer that is responsible for phosphorylating the IκBα subunit that retains p50/p65 in the cytoplasm (Step 3). When the IκBα is phosphorylated, it is ubiquitinated and degraded by the proteasome (Step 4). The p50/p65 homoclimer is imported into the nucleus (Step 5), where it activates a large number of genes (Step 6). One of these genes codes for IκBα, which sets up a negative-feedback loop by exporting p50/p65 from the nucleus (Step 7). Adapted from Trends Biochem. Sci., Vol. 30, Viatour, P., Merville, M.-P., Bours, V. and Chariot, A., Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation, pp. 4352. Copyright (2004), with permission from Elsevier; see Viatour et al. 2005.