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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Nazio F. , Carinci M. , Valacca C. , Bielli P. , Strappazzon F. , Antonioli M. , Ciccosanti F. , Rodolfo C. , Campello S. , Fimia G. M. , Sette C. , Bonaldo P. , Cecconi F.

Titolo volume/Rivista

THE JOURNAL OF CELL BIOLOGY

Anno di pubblicazione

2016

ISSN

0021-9525

ISBN

Non Disponibile

Numero di citazioni Wos

12

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

17

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile