TP53 and MTOR crosstalk to regulate cellular senescence - PubMed (original) (raw)

Editorial

TP53 and MTOR crosstalk to regulate cellular senescence

Lorenzo Galluzzi et al. Aging (Albany NY). 2010 Sep.

Abstract

The full spectrum of activities of the tumor suppressor p53 (TP53) has not been completely elucidated yet. Recently, it was demonstrated that TP53 communicates with the metabolic regulator mechanistic target of rapamycin (MTOR) to determine whether stressed cells undergo cell death, reversible quiescence or irreversible senescence, thereby adding yet another level of complexity to the signaling network that emanate from TP53.

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Figures

Figure 1.

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.

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