Chinese scientists studied ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle to reveal the regulatory mechanism of ULK1/ATG13 in mitotic autophagy and tumor growth.

This work was done by Professor ZHANG Xin and her group from High Magnetic Field Laboratory, Hefei Institutes of Physical Science.

Autophagy and cell cycle are both highly dynamic biological processes. ULK1-ATG13 is the most upstream autophagy initiation complex that is phosphorylated by mTORC1 and AMPK to induce autophagy in asynchronous conditions. However, their phospho-regulation and functions in mitosis and cell cycle remain unknown.

To tackle the problem, the team combined mass spectrometry and site-directed mutagenesis to try to figure it out.

In their work, they found that the autophagy initiation protein ULK1/ATG13 was phosphorylated by the most important kinase CDK1 in cell cycle to promote mitotic autophagy and cell cycle progression.

In addition, the team also observed that the ULK1/ATG13 complex double-knockout can not only significantly inhibit the growth of tumor cells, but also the tumor-bearing mouse model showed that the effect of tumor suppression was 95%.

This work surprised Yoshinori Ohsumi who won the 2016 Nobel Prize in Physiology or Medicine for his discovery of the mechanism of cell autophagy and the Nobel Prize owner gave his comment on the study, “a yet-unappreciated role for autophagy in cell cycle progression” and “enhances understanding of the specific phase-dependent autophagy regulation during cellular growth and proliferation” in his special review also published in PLOS Biology.

This research was funded by the National Key Research and Development Program of China, Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology, Key Program of 13th five-year plan, CASHIPS and CASHIPS Director’s Fund, National Natural Science Foundation of China and Anhui Natural Science Foundation. Corresponding author is Professor ZHANG Xin. Assistant Professor LI Zhiyuan is the first and co-corresponding author.