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Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy
Alternative autophagy is an autophagy-related protein 5 (Atg5)-independent type of macroautophagy. Unc51-like kinase 1 (Ulk1) is an essential initiator not only for Atg5-dependent canonical autophagy but also for alternative autophagy. However, the mechanism as to how Ulk1 differentially regulates b...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145817/ https://www.ncbi.nlm.nih.gov/pubmed/32273498 http://dx.doi.org/10.1038/s41467-020-15577-2 |
Sumario: | Alternative autophagy is an autophagy-related protein 5 (Atg5)-independent type of macroautophagy. Unc51-like kinase 1 (Ulk1) is an essential initiator not only for Atg5-dependent canonical autophagy but also for alternative autophagy. However, the mechanism as to how Ulk1 differentially regulates both types of autophagy has remained unclear. In this study, we identify a phosphorylation site of Ulk1 at Ser(746), which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1(746) localizes exclusively on the Golgi and is required for alternative autophagy, but not canonical autophagy. We also identify receptor-interacting protein kinase 3 (RIPK3) as the kinase responsible for genotoxic stress-induced Ulk1(746) phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser(746), and loss of RIPK3 abolishes Ulk1(746) phosphorylation. These findings indicate that RIPK3-dependent Ulk1(746) phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy. |
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