“Adaptor proteins” are necessary to link autophagosomes to proteins destined for selective degradation. One of these adaptor proteins is p62/SQSTM1. p62 is a scaffolding protein that interacts with various signaling molecules. p62 contains an LC3-interacting region and is believed to be a substrate for selective autophagy. In addition, p62 contains a domain that binds ubiquitin chains, and mediates the recruitment of poly ubiquitinated protein aggregates and depolarized mitochondria to the autophagic machinery.
There is increasing interest about impairment of autophagic degradation in neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis), alcoholic hepatitis, hepatic steatosis, and liver cancer.
■ Domain structure of p62/SQSTM1
These illustration were made under the supervision of Dr. Masaaki Komatsu and Dr. Yoshinobu Ichimura (Niigata University).
p62 has several phosphorylation sites. Two biophylaxis systems described below are effectively activated by the continuous phosphorylation on these sites.