Document Detail


p53 dynamics control cell fate.
MedLine Citation:
PMID:  22700930     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jeremy E Purvis; Kyle W Karhohs; Caroline Mock; Eric Batchelor; Alexander Loewer; Galit Lahav
Publication Detail:
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:
Title:  Science (New York, N.Y.)     Volume:  336     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-09-14     Revised Date:  2013-04-24    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1440-4     Citation Subset:  IM    
Affiliation:
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
F32GM095168/GM/NIGMS NIH HHS; GM083303/GM/NIGMS NIH HHS; R01 GM083303/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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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