Fig. 3. Cell fate decisions based on p53 concentration and cell type- and context-dependent thresholds.

Under low stress conditions, p53 protein expression is below the threshold for cell cycle arrest or apoptosis, allowing cells to proliferate. Cell cycle arrest occurs when p53 levels reach a specific threshold, defined by a tug-of-war between pro- and anti-proliferative factors, the levels of which depend on context such as cell type and nutrient availability. When p53 levels are high enough, cells undergo p53-dependent apoptosis. The threshold for apoptosis is determined by a tug-of-war between pro- and anti-apoptotic factors that vary in their abundance depending on the cellular context. Importantly, these factors represent therapeutically actionable opportunities to tip the balance toward apoptosis, a desired outcome in cancer treatment regimens.