Document Detail


Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells.
MedLine Citation:
PMID:  20598361     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tumor suppressor p53 is activated by stress and leads to cellular outcomes such as apoptosis and cell-cycle arrest. Its activation must be highly sensitive to ensure that cells react appropriately to damage. However, proliferating cells often encounter transient damage during normal growth, where cell-cycle arrest or apoptosis may be unfavorable. How does the p53 pathway achieve the right balance between high sensitivity and tolerance to intrinsic damage? Using quantitative time-lapse microscopy of individual human cells, we found that proliferating cells show spontaneous pulses of p53, which are triggered by an excitable mechanism during cell-cycle phases associated with intrinsic DNA damage. However, in the absence of sustained damage, posttranslational modifications keep p53 inactive, preventing it from inducing p21 expression and cell-cycle arrest. Our approach of quantifying basal dynamics in individual cells can now be used to study how other pathways in human cells achieve sensitivity in noisy environments.
Authors:
Alexander Loewer; Eric Batchelor; Giorgio Gaglia; Galit Lahav
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  142     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-06     Completed Date:  2010-08-02     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  89-100     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Ataxia Telangiectasia Mutated Proteins
Cell Cycle
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / genetics
DNA Damage*
DNA Repair
DNA-Binding Proteins / metabolism
Humans
Protein Processing, Post-Translational
Protein-Serine-Threonine Kinases / metabolism
Signal Transduction*
Tumor Suppressor Protein p53 / metabolism*
Tumor Suppressor Proteins / metabolism
Grant Support
ID/Acronym/Agency:
GM083303/GM/NIGMS NIH HHS; R01 GM083303/GM/NIGMS NIH HHS; R01 GM083303-01A1/GM/NIGMS NIH HHS; R01 GM083303-01A1S1/GM/NIGMS NIH HHS; R01 GM083303-02S1/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; EC 2.7.11.1/ATM protein, human; EC 2.7.11.1/Ataxia Telangiectasia Mutated Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections
Comment In:
Cell. 2010 Jul 9;142(1):17-9   [PMID:  20603009 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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