Loss of CDK4/6 activity in S/G2 phase leads to cell cycle reversal.

ABSTRACT: In mammalian cells, the decision to proliferate is thought to be irreversibly made at the restriction point of the cell cycle^1,2, when mitogen signalling engages a positive feedback loop between cyclin A2/cyclin-dependent kinase 2 (CDK2) and the retinoblastoma protein^3-5. Contrary to this textbook model, here we show that the decision to proliferate is actually fully reversible. Instead, we find that all cycling cells will exit the cell cycle in the absence of mitogens unless they make it to mitosis and divide first. This temporal competition between two fates, mitosis and cell cycle exit, arises because cyclin A2/CDK2 activity depends upon CDK4/6 activity throughout the cell cycle, not just in G1 phase. Without mitogens, mitosis is only observed when the half-life of

SUBMITTER: Cornwell JA 

PROVIDER: S-EPMC10338338 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature