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EnglishAutophagy 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.
Nazio, F., Carinci, M., Valacca, C., Bielli, P., Strappazzon, F., Antonioli, M., et al. (2016). Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation. THE JOURNAL OF CELL BIOLOGY, 215(6), 841-856.
| Tipologia: | Articolo su rivista |
| Citazione: | Nazio, F., Carinci, M., Valacca, C., Bielli, P., Strappazzon, F., Antonioli, M., et al. (2016). Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation. THE JOURNAL OF CELL BIOLOGY, 215(6), 841-856. |
| IF: | Con Impact Factor ISI |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore BIO/06 |
| Revisione (peer review): | Esperti anonimi |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1083/jcb.201605089 |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 2016 |
| Titolo: | Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation |
| Autori: | |
| Autori: | Nazio, F; Carinci, M; Valacca, C; Bielli, P; Strappazzon, F; Antonioli, M; Ciccosanti, F; Rodolfo, C; Campello, S; Fimia, GM; Sette, C; Bonaldo, P; Cecconi, F |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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