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Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy. | LitMetric

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, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1 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 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser, and loss of RIPK3 abolishes Ulk1 phosphorylation. These findings indicate that RIPK3-dependent Ulk1 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145817PMC
http://dx.doi.org/10.1038/s41467-020-15577-2DOI Listing

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