Constant rate of p53 tetramerization in response to DNA damage controls the p53
response |
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| Authors: | Giorgio Gaglia Galit Lahav |
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| Affiliation: | Department of Systems Biology, Harvard Medical School, Boston, MA, USA |
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| Abstract: | ![]()
The dynamics of the tumor suppressor protein p53 have been previously investigated in singlecells using fluorescently tagged p53. Such approach reports on the total abundance of p53 but doesnot 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. Wefound that while total p53 increases proportionally to the input strength, p53 tetramers are formedin cells at a constant rate. This breaks the linear input–output relation and dampens the p53response. Disruption of the p53-binding protein ARC led to a dose-dependent rate of tetramersformation, resulting in enhanced tetramerization and induction of p53 target genes. Our worksuggests that constraining the p53 response in face of variable inputs may protect cells fromcommitting to terminal outcomes and highlights the importance of quantifying the active form ofsignaling molecules in single cells.Quantification of the dynamics of p53 tetramers in single cells using a fluorescentprotein-fragment complementation assay reveals that, while total p53 increases proportionally to theDNA damage strength, p53 tetramers are formed at a constant rate. |
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| Keywords: | DNA damage fluorescence imaging p53 dynamics single cells tetramers |
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