Figure 1
From: The adaptor protein p62/SQSTM1 in osteoclast signaling pathways
Interaction motifs and domains of RANKL signal intermediaries. A: p62 and an aPKC. The cytosolic p62 protein, encoded by the SQSTM1 gene, is a scaffolding protein that interacts with the RANK signaling complex, and is one of the functional links reported between RANKL and TRAF-6-mediated NF-κB activation. Multiple interaction motifs located within p62 enable recruitment of specific proteins and regulation of downstream signaling pathways. RIP binds to the ZZ domain, whereas TRAF6 interacts with the TF6-b sequence, and the aPKC isoforms, ERK, and others interact with the PB1 domain. This PB1 interaction directs the aPKCs in the NF-κB pathway. The UBA domain binds to polyubiquitin chains, and is important for the ubiquitination of TRAF6. PB1, PB1 dimerisation domain; ZZ ZNF, ZZ-type zinc finger; TF6-b, TRAF6 binding sequence; PEST, (P, Proline; E, Glutamate; S, Serine; T, Threonine) rich sequence; UBA, ubiquitin associated; PS, pseudosubstrate region; MATH, meprin and TRAF homology. B: The RANK receptor. RANK has six known putative TRAF-binding motifs (PTM 1-6) of which three have been involved in osteoclast signaling. TRAF6 binds to membrane-proximal motifs such as PTM3 (PFQEP369-373), whereas PTM5 (PVQEET559-564) and PTM6 (PVQEQ604-609) most likely interact with TRAF2 and TRAF5 [22, 23]. In addition, three other TRAF6- binding sites have been identified, BS I (PTEDEY340-345), BS II (PLEVGE373-378) and BS III (PGEDHE447-452 [25, 26].