The MDM2/MDMX/p53 axis in the adaptive stress response

A proper stress response is critical for the maintenance of homeostasis. To preserve their fitness in an energetically sensible way, cells must constantly make precise decisions that range between survival and death according to the level of stress. To cope with harsh stresses that can potentially threaten their genome stability and the integrity of other essential structures, cells must sense cellular damage and promptly activate an appropriate response, such as cell cycle arrest, DNA repair, or, if the damage is unrepairable, apoptosis. However, living cells or organisms are also exposed to temporary and modest levels of stress that are more often encountered in our living environment. In response to such transient and mild stresses, arresting cell cycle progression or inducing cell death would be insensible. In this context, cells have to calibrate their stress response to the perturbation based on the level of stress. Relative to severe stress, the cellular response to mild stress is less well characterized