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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}

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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Counting the Ways to Decode Dynamic Signals.
R. Wollman (2014)
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   Abstract »    Full Text »    PDF »
Nucleocytoplasmic Shuttling of a GATA Transcription Factor Functions as a Development Timer.
H. Cai, M. Katoh-Kurasawa, T. Muramoto, B. Santhanam, Y. Long, L. Li, M. Ueda, P. A. Iglesias, G. Shaulsky, and P. N. Devreotes (2014)
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   Abstract »    Full Text »    PDF »
The regulation of MDM2 oncogene and its impact on human cancers.
Y. Zhao, H. Yu, and W. Hu (2014)
Acta Biochim Biophys Sin 46, 180-189
   Abstract »    Full Text »    PDF »
Tight Control of Hypoxia-inducible Factor-{alpha} Transient Dynamics Is Essential for Cell Survival in Hypoxia.
J. Bagnall, J. Leedale, S. E. Taylor, D. G. Spiller, M. R. H. White, K. J. Sharkey, R. N. Bearon, and V. See (2014)
J. Biol. Chem. 289, 5549-5564
   Abstract »    Full Text »    PDF »
Nested autoinhibitory feedbacks alter the resistance of homeostatic adaptive biochemical networks.
J. Schaber, A. Lapytsko, and D. Flockerzi (2014)
J R Soc Interface 11, 20130971
   Abstract »    Full Text »    PDF »
Functional Roles of Pulsing in Genetic Circuits.
J. H. Levine, Y. Lin, and M. B. Elowitz (2013)
Science 342, 1193-1200
   Abstract »    Full Text »    PDF »
Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells.
J. Y. Lee, H. J. Kim, N. A. Yoon, W. H. Lee, Y. J. Min, B. K. Ko, B. J. Lee, A. Lee, H. J. Cha, W. J. Cho, et al. (2013)
Nucleic Acids Res. 41, 5614-5625
   Abstract »    Full Text »    PDF »
Another fork in the road--life or death decisions by the tumour suppressor p53.
L. A. Carvajal and J. J. Manfredi (2013)
EMBO Rep. 14, 414-421
   Abstract »    Full Text »    PDF »
Circuit-level input integration in bacterial gene regulation.
L. Espinar, M. Dies, T. Cagatay, G. M. Suel, and J. Garcia-Ojalvo (2013)
PNAS 110, 7091-7096
   Abstract »    Full Text »    PDF »
Rate of environmental change determines stress response specificity.
J. W. Young, J. C. W. Locke, and M. B. Elowitz (2013)
PNAS 110, 4140-4145
   Abstract »    Full Text »    PDF »
Therapeutic Hints from Analyzing the Attractor Landscape of the p53 Regulatory Circuit.
W. Wang (2013)
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   Abstract »    Full Text »    PDF »
Tunable Signal Processing Through Modular Control of Transcription Factor Translocation.
N. Hao, B. A. Budnik, J. Gunawardena, and E. K. O'Shea (2013)
Science 339, 460-464
   Abstract »    Full Text »    PDF »
Direct observation of frequency modulated transcription in single cells using light activation.
D. R. Larson, C. Fritzsch, L. Sun, X. Meng, D. S. Lawrence, and R. H. Singer (2013)
eLife Sci 2, e00750
   Abstract »    Full Text »    PDF »
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T. A. Sutton, T. Hato, E. Mai, M. Yoshimoto, S. Kuehl, M. Anderson, H. Mang, Z. Plotkin, R. J. Chan, and P. C. Dagher (2013)
J. Am. Soc. Nephrol. 24, 113-124
   Abstract »    Full Text »    PDF »
Attractor Landscape Analysis Reveals Feedback Loops in the p53 Network That Control the Cellular Response to DNA Damage.
M. Choi, J. Shi, S. H. Jung, X. Chen, and K.-H. Cho (2012)
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   Abstract »    Full Text »    PDF »
Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity.
N. Hao, N. Yildirim, M. J. Nagiec, S. C. Parnell, B. Errede, H. G. Dohlman, and T. C. Elston (2012)
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