Review Article

Autophagy and Its Role in Protein Secretion: Implications for Cancer Therapy

Figure 1

A general overview of the autophagic pathway and its regulators. In mammals, the ULK1/2 kinase complex regulates autophagosome initiation. ULK1/2 is regulated by nutrient sensing or stress signaling by mTOR complex 1, which inhibits autophagy in the presence of amino acids or insulin/PI3K/AKT signaling. ULK1/2 is also regulated by AMPK, which is activated by high AMP/low ATP levels. Activated ULK1/2 then phosphorylates and activates components of the class III PI3K nucleation complex responsible for the formation of PI3P and for the recruitment of PI3P-binding proteins. Vesicle elongation is mediated by two ubiquitin-like protein conjugation systems: ATG5-ATG12 and LC3-PE. Once the autophagosome is formed, it fuses with the lysosomes and their contents are degraded. The figure shows pharmacological regulators of autophagy mentioned in the text (ATG: autophagy related; mTOR: mechanistic target of rapamycin; PI3K: phosphatidylinositol 3-kinase; PE: phosphatidylethanolamine; PI3P: phosphatidylinositol 3-phosphate; AMPK: AMP-activated protein kinase; 3MA: 3-methyl adenine).