An intermediate Rb-E2F activity state safeguards proliferation commitment.

ABSTRACT: Tissue repair, immune defence and cancer progression rely on a vital cellular decision between quiescence and proliferation^1,2. Mammalian cells proliferate by triggering a positive feedback mechanism^3,4. The transcription factor E2F activates cyclin-dependent kinase 2 (CDK2), which in turn phosphorylates and inactivates the E2F inhibitor protein retinoblastoma (Rb). This action further increases E2F activity to express genes needed for proliferation. Given that positive feedback can inadvertently amplify small signals, understanding how cells keep this positive feedback in check remains a puzzle. Here we measured E2F and CDK2 signal changes in single cells and found that the positive feedback mechanism engages only late in G1 phase. Cells spend variable and often exte

SUBMITTER: Konagaya Y 

PROVIDER: S-EPMC11236703 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature