NOVEL AUTOPHAGY REGULATORS ATG14L AND RUBICON

摘要

The present invention provides for up- and down- regulation of cellular autophagy, e.g., for treating cancer or neurological disease. The invention results, in part, from discovery of two novel proteins, ATGl 4L (previously called "BISC") and Rubicon (previously called "BIRC"), which bind to a Class III phophatidylinositol 3'- kinase (PI3K)/Vps34-Beclin 1 autophagic complex. ATG 14L and Rubicon each regulate autophagic activity in an opposing manner. ATG 14L and Rubicon can be used, for example, to increase/decrease autophagic activity, to increase/decrease PI3K7Vps34 kinase activity, and in so doing, treat diseases and disorders, such as cancer, neurodegenerative disease, stroke, metabolic disease, and age-related disease. ATG14L can increase autophagic activity and PI3K/Vps34 kinase activity; and Rubicon can decrease autophagic activity and PI3K/Vps34 kinase activity.