Mechanisms of Autophagy
The ubiquitin-conjugating protein p62/SQSTM1 is thought to be a scaffold protein that interacts with a variety of molecules involved in toll-like receptor (TLR) signaling, such as TRAF6, ERK, and aPKC. Recent evidence suggests that p62 binds directly to the autophagosome marker LC3 and is then selectively degraded by autophagy.
p62 contains multiple phosphorylation sites. Sequential phosphorylation of these sites regulates biological defense mechanisms such as selective autophagy and the Keap1-Nrf2 system. Therefore, the failure of the p62 pathway is associated with various diseases such as cancer and many neurodegenerative diseases.