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dc.contributor.authorGaglia, Giorgioen_US
dc.contributor.authorLahav, Galiten_US
dc.date.accessioned2015-02-02T15:31:32Z
dc.date.issued2014en_US
dc.identifier.citationGaglia, Giorgio, and Galit Lahav. 2014. “Constant rate of p53 tetramerization in response to DNA damage controls the p53 response.” Molecular Systems Biology 10 (10): 1-8. doi:10.15252/msb.20145168. http://dx.doi.org/10.15252/msb.20145168.en
dc.identifier.issn1744-4292en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13890589
dc.description.abstractThe dynamics of the tumor suppressor protein p53 have been previously investigated in single cells using fluorescently tagged p53. Such approach reports on the total abundance of p53 but does not provide a measure for functional p53. We used fluorescent protein-fragment complementation assay (PCA) to quantify in single cells the dynamics of p53 tetramers, the functional units of p53. We found that while total p53 increases proportionally to the input strength, p53 tetramers are formed in cells at a constant rate. This breaks the linear input–output relation and dampens the p53 response. Disruption of the p53-binding protein ARC led to a dose-dependent rate of tetramers formation, resulting in enhanced tetramerization and induction of p53 target genes. Our work suggests that constraining the p53 response in face of variable inputs may protect cells from committing to terminal outcomes and highlights the importance of quantifying the active form of signaling molecules in single cells. Quantification of the dynamics of p53 tetramers in single cells using a fluorescent protein-fragment complementation assay reveals that, while total p53 increases proportionally to the DNA damage strength, p53 tetramers are formed at a constant rate.en
dc.language.isoen_USen
dc.publisherBlackWell Publishing Ltden
dc.relation.isversionofdoi:10.15252/msb.20145168en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299375/pdf/en
dash.licenseLAAen_US
dc.subjectDNA damageen
dc.subjectfluorescence imagingen
dc.subjectp53 dynamicsen
dc.subjectsingle cellsen
dc.subjecttetramersen
dc.titleConstant rate of p53 tetramerization in response to DNA damage controls the p53 responseen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalMolecular Systems Biologyen
dash.depositing.authorLahav, Galiten_US
dc.date.available2015-02-02T15:31:32Z
dc.identifier.doi10.15252/msb.20145168*
dash.contributor.affiliatedLahav, Galit


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