Mitotic phosphorylation of the ULK complex regulates cell cycle progression

PLoS Biol. 2020 Jun 9;18(6):e3000718. doi: 10.1371/journal.pbio.3000718. eCollection 2020 Jun.

Abstract

Autophagy is an intracellular degradation pathway targeting organelles and macromolecules, thereby regulating various cellular functions. Phosphorylation is a key posttranscriptional protein modification implicated in the regulation of biological function including autophagy. Under asynchronous conditions, autophagy activity is predominantly suppressed by mechanistic target of rapamycin (mTOR) kinase, but whether autophagy-related genes (ATG) proteins are phosphorylated differentially throughout the sequential phases of the cell cycle remains unclear. In this issue, Li and colleagues report that cyclin-dependent kinase 1 (CDK1) phosphorylates the ULK complex during mitosis. This phosphorylation induces autophagy and, surprisingly, is shown to drive cell cycle progression. This work reveals a yet-unappreciated role for autophagy in cell cycle progression and enhances our understanding of the specific phase-dependent autophagy regulation during cellular growth and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Autophagy*
  • CDC2 Protein Kinase*
  • Mechanistic Target of Rapamycin Complex 1
  • Mitosis
  • Phosphorylation
  • TOR Serine-Threonine Kinases

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • CDC2 Protein Kinase

Grants and funding

This work was supported in part by JSPS KAKENHI grants (https://www.jsps.go.jp/english/index.html) 17K18339 (to A.Y.), 18K06211 (to Y.J.), and 16H06375 (to Y.O.); and the Takeda Science Foundation (https://www.takeda-sci.or.jp) (to A.Y.) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.