The Role of the Selective Adaptor p62 and Ubiquitin-Like Proteins in Autophagy

Figure 5

Domain structure of p62 and its interacting partners. There are six main domains/motifs in the p62 protein, necessary for its interaction with the autophagic machinery and with signaling pathways. The N-terminal Phox and Bem1 (PB1, 21-103 aa) domain is involved in the self-oligomerization of p62 or in heterodimerization with NBR1, a protein similar to p62. The PB1 domain is also responsible for the binding to atypical PKC (aPKC) or to ERK1. The central zinc finger ZZ domain (128-163 aa) and the TRAF6-binding domain (TB, 225-250 aa) interact with the RIP and TRAF6 proteins, respectively, to regulate the NF-κB pathway. Through the LC3-interacting region (LIR, 321-345 aa) and the C-terminal ubiquitin-associated domain (UBA, 386-440 aa), p62 links the autophagic machinery to ubiquitinylated protein substrates to promote the selective degradation of these molecules. Finally, the Keap-interacting region (KIR, 346-359 aa) binds Keap1 leading to stabilization and nuclear translocation of the transcription factor Nrf2, engaged in the control of ROS level.