What is the function of p62?

What is the function of p62?

The central function of p62 is involved in the degradation of misfolded proteins through UPS or the autophagy-lysosome pathway. These two pathways are the major self-regulating systems to degrade misfolded protein aggregation and maintain the cellular homeostasis in eukaryotic cells.

What is the role of p62 in autophagy?

p62, a classical receptor of autophagy, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1–Nrf2 pathway. It is involved in the proteasomal degradation of ubiquitinated proteins.

What is p62 gene?

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy.

What is p62 protein?

p62 is a multifunctional protein that facilitates protein degradation through autophagy and the ubiquitin-proteasome system, and also regulates cell survival via the Nrf2 antioxidant response pathway, the nuclear factor-kappa B signaling pathway and apoptosis.

Is p62 degraded by the proteasome?

However, p62 itself was not degraded by the proteasome (34). The core autophagy protein ATG16 also appears to play a modulatory role between the UPS and autophagy. ATG16 was known to be an essential component of the ATG complex, and the ATG12-ATG5 complex binds to ATG16 for the phagophore formation (35).

Is p62 a marker of autophagy?

Since p62 accumulates when autophagy is inhibited, and decreased levels can be observed when autophagy is induced, p62 may be used as a marker to study autophagic flux.

What is LC3 autophagy?

LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.

What proteins are degraded in the proteasome?

This tagging process leads to their recognition by the 26S proteasome, a very large multicatalytic protease complex that degrades ubiquitinated proteins to small peptides (10).

What does it mean if a protein is ubiquitinated?

Ubiquitination is a small (76-amino acid) protein that is highly conserved and widely expressed in all eukaryotic cells. Ubiquitination involves one or more covalent additions to the lysine residues of target proteins.

What is LC3-I and LC3-II?

It is known to exist in two forms: LC3-I, which is found in the cytoplasm, and LC3-II, which is membrane-bound and is converted from LC3-I to initiate formation and lengthening of the autophagosome. It differs from LC3-I only in the fact that it is covalently modified with lipid extensions (lipidation).

What is the role of LC3?

Henceforth, LC3 has been widely used to monitor the number of autophagosomes as well as autophagic activity. Moreover, emerging evidence has shown that during selective autophagy, LC3 functions as an adaptor protein to recruit selective cargo to the autophagosome via interaction with cargo receptors (7).

What is the role of proteasomes in protein degradation?

The proteasome is one of the major degradation machineries in eukaryotic cells. It terminates the existence of thousands of short-lived, damaged, misfolded or otherwise obsolete proteins and plays pivotal roles in protein quality control and other vital processes in the cell.

What is the difference between phagosome and lysosome?

The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS.

What amino acids are ubiquitinated?

Ubiquitin has seven lysine residues and an N-terminus that serves as points of ubiquitination; they are K6, K11, K27, K29, K33, K48, K63 and M1, respectively. Lysine 48-linked chains were the first identified and are the best-characterised type of ubiquitin chain.

Which amino acids are ubiquitinated?

Which functional domains of p62 are associated with ubiquitinated protein degradation?

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.

What is the p62 protein?

The p62 protein is a beautiful paradigm for complexity in molecular biology. Via its domain structure, p62 interacts with several proteins regulating key pathways required for the maintenance of homeostasis of cells and tissues, as well as for inflammation and common diseases including cancer ( Figure 4 ).

How is p62 binding to its numerous interaction partners regulated?

Although research in the past has revealed that p62 is modified and regulated by phosphorylation, ubiquitination, acetylation, proteolytic processing, and the formation of disulfide bridges, we are far away from precisely understanding how the binding of p62 to its numerous interaction partners is regulated.

Why is the PB1 domain of p62 required for autophagy?

The amino terminal PB1 domain (Phox1 and Bem1p) of p62 is required for the homotypic oligomerization of inactive p62 dimers, which results in a helical structure required for its role as a cargo receptor in autophagy [ 36 ].