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

Author

Listed:
  • Satoru Torii

    (Tokyo Medical and Dental University (TMDU))

  • Hirofumi Yamaguchi

    (Tokyo Medical and Dental University (TMDU))

  • Akira Nakanishi

    (Tokyo Medical and Dental University (TMDU))

  • Satoko Arakawa

    (Tokyo Medical and Dental University (TMDU))

  • Shinya Honda

    (Tokyo Medical and Dental University (TMDU))

  • Kenta Moriwaki

    (Osaka University)

  • Hiroyasu Nakano

    (Toho University School of Medicine)

  • Shigeomi Shimizu

    (Tokyo Medical and Dental University (TMDU))

Abstract

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.

Suggested Citation

  • Satoru Torii & Hirofumi Yamaguchi & Akira Nakanishi & Satoko Arakawa & Shinya Honda & Kenta Moriwaki & Hiroyasu Nakano & Shigeomi Shimizu, 2020. "Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15577-2
    DOI: 10.1038/s41467-020-15577-2
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