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Science 336 (6087): 1440-1444

Copyright © 2012 by the American Association for the Advancement of Science

p53 Dynamics Control Cell Fate

Jeremy E. Purvis, Kyle W. Karhohs, Caroline Mock, Eric Batchelor,* Alexander Loewer,{dagger} Galit Lahav{ddagger}

Abstract: Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.

Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

* Present address: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

{dagger} Present address: Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin-Buch 13125, Germany.

{ddagger} To whom correspondence should be addressed. E-mail: galit{at}hms.harvard.edu


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