Unknown

Dataset Information

0

Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation.


ABSTRACT: Autophagy is an intracellular degradation pathway whose levels are tightly controlled to secure cell homeostasis. Unc-51-like kinase 1 (ULK1) is a conserved serine-threonine kinase that plays a central role in the initiation of autophagy. Here, we report that upon autophagy progression, ULK1 protein levels are specifically down-regulated by the E3 ligase NEDD4L, which ubiquitylates ULK1 for degradation by the proteasome. However, whereas ULK1 protein is degraded, ULK1 mRNA is actively transcribed. Upon reactivation of mTOR-dependent protein synthesis, basal levels of ULK1 are promptly restored, but the activity of newly synthesized ULK1 is inhibited by mTOR. This prepares the cell for a new possible round of autophagy stimulation. Our results thus place NEDD4L and ULK1 in a key position to control oscillatory activation of autophagy during prolonged stress to keep the levels of this process under a safe and physiological threshold.

PROVIDER: S-EPMC5166502 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC6971022 | BioStudies
1000-01-01 | S-EPMC5290961 | BioStudies
1000-01-01 | S-EPMC2663915 | BioStudies
2018-01-01 | S-EPMC6103675 | BioStudies
1000-01-01 | S-EPMC4590650 | BioStudies
| S-EPMC4530630 | BioStudies
2018-01-01 | S-EPMC5891421 | BioStudies
| S-EPMC3987946 | BioStudies
1000-01-01 | S-EPMC4590663 | BioStudies
2017-01-01 | S-EPMC5646326 | BioStudies