Interaction Domains of p62: A Bridge Between p62 and Selective Autophagy

Abstract

p62 is a multidomain protein that contains different kinds of protein-protein interaction domains, including an N-terminal PB1 domain, a ZZ-type zinc finger domain, a nuclear localization signal (NLS), an export motif (NES), the LC3-interacting region (LIR), the KEAP1-interacting region (KIR), and a C-terminal Ub-associated domain (UBA). p62 is involved in the degradation of protein aggregates and cytoplasmic bodies via selective autophagy through its PB1, LIR, and UBA domains to maintain homeostasis in the cell. Moreover, NES, NLS, KIR, and ZZ domains have been found to be linked to ubiquitinated protein degradation by autophagy. Therefore, understanding the functional domains of p62 is important. In this review, we attempt to expound the mechanism of connection between p62 and selective autophagy to illustrate how the domains of p62 regulate selective autophagy, and to provide a new direction and perspective on selective autophagy research.

Redox regulation of mitophagy in the lung during murine Staphylococcus aureus sepsis

“…Recent evidence has highlighted the importance of p62/sequestosome 1/SQSTM1 protein in the selective degradation of ubiquinated proteins [48–50]. This protein binds directly to LC3-II through its LC3-interacting region (LIR) which ultimately results in lysosomal degradation of proteins [51]. Earlier observations of mitophagy have emphasized that during collapse of membrane potential and generation of excess ROS, mitochondria are disposed of by p62-dependent pathways [52,53].…”

Routine Western blot to check autophagic flux: Cautions and recommendations

“…However, the use of p62 levels as a measurement of cargo degradation has already been 353 questioned [4] because of the recently discovered association between p62 and multiple proteins 354 involved in several biological processes [13] . Moreover, solubility problems have been described 355 in relation to the non-solubility of p62 aggresomes when using common non-ionic detergents, 356 such as Triton X-100 [4] .…”

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

“…Kelch-like ECH-associated protein (Keap1) works as an adaptor for E3 ligase and initiates proteasomal degradation of several proteins. Treatment of liver cells with PA resulted in decreased Keap1 cellular levels as the result of an increased Keap1 degradation through autophagy by a p62 dependent mechanism 78, 79 . In addition, short hairpin RNA-mediated knockdown of Keap1 resulted in upregulation of BIM and PUMA, leading to hepatocyte apoptosis 80 (Table 1).…”