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Title:
Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy | Nature Communications
Description:
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 Ser746, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1746 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 Ulk1746 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser746, and loss of RIPK3 abolishes Ulk1746 phosphorylation. These findings indicate that RIPK3-dependent Ulk1746 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy. Unlike canonical macroautophagy, alternative autophagy does not require the factors Atg5 and Atg7, but does require Ulk1. Here the authors show that phosphorylation of Ulk1 at Ser746 by RIPK3 is required for alternative autophagy initiation at the Golgi in response to genotoxic stress.
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Keywords {π}
autophagy, fig, ulk, mefs, etoposide, alternative, ripk, cells, phosphorylation, ser, treatment, pulk, supplementary, data, atgko, article, signals, cell, golgi, treated, atgripkdko, canonical, shown, performed, puncta, antibody, haulk, analyzed, images, red, google, scholar, cas, etoposideinduced, source, min, genotoxic, protein, observed, expression, analysis, nature, atgulkdko, image, vsvggfp, kinase, tcz, lamp, similar, research,
Topics {βοΈ}
nature portfolio privacy policy author information authors bcl-xl/bcl-2 targeting compound pan-caspase inhibitor q-vd-oph advertising atg5/atg7-independent alternative macroautophagy phospho-thr/phospho-ser/met social media joint usage/research program references mizushima reprints nature 451 nature 461 nature 533 nature data availability pan-caspase inhibitor zvad mcherry-gfp-lc3-expressing cells atg5-independent alternative macroautophagy atg5/ulk1/ulk2 triple-knockout mrfpβgfp-expressing atg5ko mefs ripk3-dependent p-ulk1746 signals etoposide-induced p-ulk1746 signals tukey post-hoc test reversed-phase c18 column hiq sil c18w-3p additional kinases vsvgβgfp-expressing atg5ko mefs tailed student t-tests scientific research upper figures thin sections genotoxic stress-induced alterations c-terminal fragment ions n-terminal fragment ions atg5/ulk1dko mef derivatives original author phospho-ulk1746 localizes exclusively p53βripk3-dependent ulk1746 phosphorylation stimulus/context-dependent manner etoposide-induced p-ulk1746 generation p-ulk1746 localizes solely expressing atg5/ulk1dko mefs blocks rapamycin-induced autophagy16 laser-scanning confocal microscope peer review atg5/p53 double-knockout genotoxic stress-induced autophagy anti-ulk1/anti-gs28 antibodies
Questions {β}
- How does etoposide induce RIPK3-mediated Ulk1746 phosphorylation?
- How does p-Ulk1746 localize on the Golgi?
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headline:Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy
description: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 Ser746, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1746 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 Ulk1746 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser746, and loss of RIPK3 abolishes Ulk1746 phosphorylation. These findings indicate that RIPK3-dependent Ulk1746 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy. Unlike canonical macroautophagy, alternative autophagy does not require the factors Atg5 and Atg7, but does require Ulk1. Here the authors show that phosphorylation of Ulk1 at Ser746 by RIPK3 is required for alternative autophagy initiation at the Golgi in response to genotoxic stress.
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headline:Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy
description: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 Ser746, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1746 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 Ulk1746 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser746, and loss of RIPK3 abolishes Ulk1746 phosphorylation. These findings indicate that RIPK3-dependent Ulk1746 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy. Unlike canonical macroautophagy, alternative autophagy does not require the factors Atg5 and Atg7, but does require Ulk1. Here the authors show that phosphorylation of Ulk1 at Ser746 by RIPK3 is required for alternative autophagy initiation at the Golgi in response to genotoxic stress.
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