Mitotic phosphorylation of the ULK complex regulates cell cycle progression

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.

TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle

“…On the other hand, it becomes increasingly apparent that growth-controlling signaling pathways are in direct, bidirectional communication with the cell-cycle machinery (Moreno-Torres et al, 2017Odle et al, 2020;Romero-Pozuelo et al, 2020;Talarek et al, 2017). It will therefore be instructive to investigate further whether the activity of TORC1 and PKA towards catabolic processes such as autophagy is also coordinated with the cell cycle, as recent evidence suggests (Li et al, 2020;Odle et al, 2020;Yamasaki et al, 2020). Untangling the complex interactions of these fundamental intracellular processes will provide a much deeper understanding of how proliferating cells coordinate growth with division.…”

Spatially Resolved Phosphoproteomics Reveals Fibroblast Growth Factor Receptor Recycling-driven Regulation of Autophagy and Survival

“…The G1/S checkpoint is known to be controlled by the homeostatic balances of nutrients, such as amino acids and sugars, all regulating mTOR signalling 78 . Thus, FGF10 may specifically alter the balance at this checkpoint by supressing the negative regulation of autophagy on cell cycle progression via mTOR/ULK1 during receptor recycling [78][79][80] . Alternatively, FGF signalling could regulate the link between cell cycle, number, and size by controlling the activation of CDKs, mTOR, and MAPKs, respectively 81 .…”

Research progress on astrocyte autophagy in ischemic stroke

“…Initially, the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) and the energy sensor AMP-dependent protein kinase (AMPK) serve as upstream regulators of autophagy and modulate the critical autophagy-initiating kinase Unc-51-like autophagy-activating kinase 1 (ULK1), inducing autophagy ( 16 – 18 ). The protein kinase ULK complex is composed of ULK1/2, FIP200, ATG13, and ATG101 ( 19 ), and the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1) consisting of PIK3C3/vacuolar protein sorting 34 (VPS34), PIK3R4/VPS15, Beclin1, and ATG14L are then successively translocated and recruited to the phosphatidylinositol synthase (PIS)-rich ER subregion which consequently drives the autophagy cascade ( 20 – 22 ).…”