Activation of the NF-κB pathway by IL-1. IL-1 binds to its receptor (IL-1R1) and receptor-associated protein (IL-1RAcP), causing conformational changes in multiple receptor-bound proteins (MyD88, IRAK, TRAF6, TAB2; see Figure 1 for definition). This results in recruitment and activation of transforming-growth-factor-κ-activated kinase-1 (TAK 1), which phosphorylates and activates NF-κB-inducing kinase (NIK). In turn, NIK activates the inhibitor of κB kinase (IKK) complex, which is responsible for phosphorylation of inhibitor of κB (IκB) and NF-κB1 (a 105 kDa protein, p105). Upon phosphorylation, IκB and p105 become polyubiquitinated (U), which targets these proteins for degradation by the proteosome. Degradation of these cellular inhibitors allows translocation of NF-κB subunits to translocate to the nucleus and transactivate matrix metalloproteinase (MMP) promoters. The IκB-like protein, Bcl-3, promotes dimerization of the 50 kDa NF-κB subunit (p50) and regulates the transcriptional activity of p50.