Editorial Volume 2, Issue 9 pp 535—537

Figure 1. TP53 levels determine whether CDKN1A will orchestrate irreversible senescence or quiescence. (A) Low doses of doxorubicin are sufficient to trigger TP53-mediated transactivation of the cell cycle-arresting protein CDKN1A. Under conditions in which the MTOR pathway is active, prolonged cell cycle arrest results in irreversible senescence. (B) High doxorubicin concentrations (or nutlin-3a alone or in combination with low doses of doxorubicin) not only drive TP53-mediated CDKN1A transactivation but might also result in the induction of one (or more) senescence-suppressing factors. In this scenario, MTOR activity is suppressed and CDKN1A-mediated cell cycle arrest is reversible (quiescence). By pharmacologically inhibiting MTOR, rapamycin also exerts senescence-suppressing functions.