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A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B

Pengo, N., Agrotis, A., Prak, K., Jones, J., Ketteler, R.·2017·Nature Communications
DOI 10.1038/s41467-017-00303-2PMC PMC5562857
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Abstract

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing.

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Metadata

Authors
Pengo, N., Agrotis, A., Prak, K., Jones, J., & Ketteler, R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-08-18
Volume
8
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-017-00303-2
PMC
PMC5562857
Cited by
148
References
5
Language
en
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