Phospho-regulation and function of ULK1-ATG13 during the cell cycle.

Although it has been reported that some autophagy-related proteins could regulate the cell cycle, the function of ULK1-ATG13, the only protein kinase complex in macroautophagy/autophagy, remains unclear. We recently found that mitotic ULK1 and ATG13 are both substrates of the key cell cycle regulator CDK1-CCNB/cyclin B. CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression. Moreover, ULK1 and ATG13 double-knockout significantly inhibits cell cycle progression and tumor cell proliferation in vitro and in vivo. These findings bridge the mutual regulation between autophagic and mitotic key kinases and provide a theoretical basis for autophagy- and cell division-related diseases based on combination therapy.