ATG12

By Jamshed Arslan, Pharm. D., PhD.

By Christina Towers, PhD

By Christina Towers, PhD

By Christina Towers, PhD

By Christina Towers, PhD.

WD repeat domain phosphoinositide-interacting protein 1 (WIPI) is involved in the lysosomal degradation of cytoplasmic components during starvation-induced autophagy. WIPI1 is a seven bladed beta-propeller protein that provides a scaffold for the assembly of multimeric protein complexes (1). During the assembly of the autophagosome WIPI1 interacts with the lipid phosphatidylinositol-3 phosphate (PI3P) and mediates the recruitment of the large multimeric complex of ATG12-ATG5-ATG16 (1).

Autophagy is an important cellular process that maintains homeostasis by degrading and recycling damaged proteins and organelles. Autophagy receptors, such as p62/SQSTM1, recognize these intracellular cargo and mediate their engulfment by the double-membrane autophagosome. The autophagosomes are subsequently targeted to the lysosome for degradation. An early regulatory step in this process is the activation and lipidation of ATG8 related proteins such as microtubule-associated protein-1 light chain 3 (LC3).

Autophagy is a process by which cells degrade and recycle damaged organelles or misfolded proteins. These various cargo are engulfed in a double-membrane structure called the autophagosome. The autophagosome then fuses with the lysosome to facilitate the degradation of the cargo. This process requires the concerted effort of an extensive network of proteins. One of the early steps of autophagosome assembly is the formation of the large multimeric ATG12-ATG5-ATG16 complex.

Autophagy is an essential cellular process whereby damaged proteins and organelles are degraded and recycled. Autophagy, while happening constantly at a basal level, is tightly regulated and can be further induced under cellular stress. One of the regulators of the early steps of autophagy is ATG4. The ATG4 family of cysteine proteases consists of 4 homologs: ATG4A, ATG4B, ATG4C, and ATG4D.

Autophagy can be broken down into 4 main stages: phagophore nucleation, autophagosome elongation, autophagosome docking and fusion with a lysosome, and vesicle breakdown and degradation. ATG4B is one of four ATG4 homologs (ATG4A, ATG4B, ATG4C, and ATG4D) involved in autophagosome elongation. ATG4B encodes a 48 kDa protein called autophagin-1 that is a member of the C54 family of cysteine proteases.