Figure 3.

RANKL signaling induces TRAF3 degradation to promote osteoclast formation. A TRAF3/TRAF2/cIAP complex constitutively induces ubiquitination (Ub) and proteasomal degradation of NIK in unstimulated osteoclast precursors. As a consequence, p100 and RelB remain in the cytoplasm in an inactive complex with the inhibitory NF-κB protein, IKKα (left panel). RANKL binding to RANK induces ubiquitination and autophagolysosomal degradation of TRAF3, allowing accumulation of NIK, which phosphorylates and activates IKKα. IKKα then phosphorylates p100, leading to its proteasomal processing to p52. As a result, p52/RelB dimers translocate to the nucleus of osteoclast precursors to promote osteoclast formation (right panel).