ULK1

ULK1 is the mammalian ortholog of yeast Atg1 and the apical kinase that launches autophagosome formation. It assembles with ATG13, FIP200 and ATG101 into the ULK1 complex, which is activated when nutrient-rich conditions withdraw mTORC1 inhibition and when AMPK phosphorylates ULK1 during energy stress. Active ULK1 phosphorylates itself, its complex partners, and components of the class III PI3K machinery such as Beclin-1 and ATG14, nucleating autophagy at phagophore assembly sites. ULK1 is essential for stress adaptation, development and neuronal homeostasis, and is a prominent target in cancer, neurodegeneration and immunity. Recombinant ULK1 underpins autophagy-kinase assays and inhibitor discovery.