Transient activation of AMP-activated protein kinase at G1/S phase transition is required for control of S phase in...

AMP-activated protein kinase (AMPK) functions as a cellular energy sensor by monitoring the cellular AMP:ATP ratio and plays a central role in cellular and whole-body energy homeostasis. Recent studies have suggested that AMPK also contribute to cell cycle regulation, but its role in this field remains almost elusive. In the present study, we report that AMPKα1 was transiently activated during G₁/S transition phase in NIH3T3 cells in the absence of any metabolic stress. Inhibition of AMPK activity at G₁/S transition phase completely blocked cells from entering S phase; in contrast, persistent activation of AMPK at G₁/S transition phase allowed cells to normally enter S phase, but these cells failed to proceed to G₂/M phase, stacking at S phase. We further demonstrated that activation of AMPK at G₁/S transition phase depends on Ca²⁺ transients and CaMKKβ activity, but not on energy status. Collectively, these data indicate that temporal regulation of AMPK is required for proper control of S phase in NIH3T3 cells.