| p53 dynamics control cell fate. | |
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MedLine Citation:
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PMID: 22700930 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jeremy E Purvis; Kyle W Karhohs; Caroline Mock; Eric Batchelor; Alexander Loewer; Galit Lahav |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 336 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-06-15 Completed Date: 2012-09-14 Revised Date: 2013-04-24 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1440-4 Citation Subset: IM |
Affiliation:
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Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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genetics Cell Aging / genetics* Cell Cycle Checkpoints Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p21 / genetics DNA Breaks, Double-Stranded* DNA Repair Gamma Rays Humans Imidazoles / metabolism, pharmacology Models, Biological Nuclear Proteins / genetics Piperazines / metabolism, pharmacology Signal Transduction* Single-Cell Analysis Transcription Factors / genetics Transcriptional Activation Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / genetics |
| Grant Support | |
ID/Acronym/Agency:
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F32GM095168/GM/NIGMS NIH HHS; GM083303/GM/NIGMS NIH HHS; R01 GM083303/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Imidazoles; 0/Nuclear Proteins; 0/Piperazines; 0/TP53 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 0/nutlin 3; 143220-95-5/PML protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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