CRL4AMBRA1 Is a Key Mediator for AKT-dependent Cell Cycle Control in Neural Progenitor Cells

ABSTRACT: Neural progenitor cell (NPC) proliferation is fundamental for population expansion and brain development. G1 phase control determines the cell cycle duration of NPCs and thereby affects their proliferation efficiency. However, the molecular mechanisms governing G1 phase progression in NPCs remain unclear. Here, we show that AKT gain-of-function mutations and pharmacological inhibition exert opposing effects on NPC proliferation. Consistently, Emx1-Cre-mediated deletion of Akt1/2/3 in mice impairs NPC proliferation and disrupts cortical development. We find that AKT deficiency induces G1 phase arrest and prolongs the cell cycle of NPCs. Mechanistically, we demonstrate that AKT-mediated phosphorylation inhibits the activity of CRL4AMBRA1 E3 ubiquitin ligase to safeguard cyclin D2 (CCND2) sta

SUBMITTER: He Wang 

PROVIDER: S-SCDT-10_1038-S44319-026-00768-7 | biostudies-other |

REPOSITORIES: biostudies-other