ULK1 Inhibits the FBXW5-dependent degradation of Sec23B to promote Autophagy

MARIO ROSSI

Conferencia; ICGEB Workshop on autophagy 2017; 2017

Sec23B is a component of the Coat Protein Complex II (COPII), which has recently been shown to provide a membrane source for the LC3 lipidation step of autophagosome biogenesis. However, the molecular mechanisms regulating COPII components in respect to autophagy are not well understood. Here, we show that the F-box protein FBXW5 targets Sec23B for proteosomal degradation and that this event limits the autophagic flux under unstressed conditions. In response to nutrient starvation, ULK1-mediated phosphorylation of Sec23B on Serine 186 prevents the interaction of Sec23B with FBXW5 and its consequent degradation while preserving its ability to associates with other COPII components. Moreover, the fraction of Sec23B that is phosphorylated and stabilized associates with Sec24A and Sec24B, but not Sec24C and Sec24D, consistent with the observation that Sec24A and Sec24B play a specific role in the regulation of the autophagic flux. In summary, we identified a biochemical pathway that controls the abundance of Sec23B to keep autophagy in check in basal conditions and ensure efficient execution of the autophagic cascade in response to nutrient starvation.