Cell cycle regulation by the ribotoxic stress response

Cells must sense and respond to numerous stimuli to maintain their function. Stress-activated protein kinases (SAPKs) are part of an integrated network that responds to these stimuli and have critical roles in determining cell behavior. Over the past 5 years, ribosomes and the ribotoxic stress response (RSR) have unexpectedly emerged as critical regulators of the SAPK network and drivers of global cell fate changes. In particular, RSR-SAPK signaling has potent effects on cellular proliferation, with important implications for senescence and cancer. In this review, we discuss cell cycle regulation by the SAPK p38, with a particular focus on how ribotoxic stress affects key cell cycle transitions.