The DNA binding activity of p53 displays reaction-diffusion kinetics.

Hinow P, Rogers CE, Barbieri CE, Pietenpol JA, Kenworthy AK, DiBenedetto E
Biophys J. 2006 91 (1): 330-42

PMID: 16603489 · PMCID: PMC1479054 · DOI:10.1529/biophysj.105.078303

The tumor suppressor protein p53 plays a key role in maintaining the genomic stability of mammalian cells and preventing malignant transformation. In this study, we investigated the intracellular diffusion of a p53-GFP fusion protein using confocal fluorescence recovery after photobleaching. We show that the diffusion of p53-GFP within the nucleus is well described by a mathematical model for diffusion of particles that bind temporarily to a spatially homogeneous immobile structure with binding and release rates k1 and k2, respectively. The diffusion constant of p53-GFP was estimated to be Dp53-GFP=15.4 microm2 s-1, significantly slower than that of GFP alone, DGFP=41.6 microm2 s-1. The reaction rates of the binding and unbinding of p53-GFP were estimated as k1=0.3 s-1 and k2=0.4 s-1, respectively, values suggestive of nonspecific binding. Consistent with this finding, the diffusional mobilities of tumor-derived sequence-specific DNA binding mutants of p53 were indistinguishable from that of the wild-type protein. These data are consistent with a model in which, under steady-state conditions, p53 is latent and continuously scans DNA, requiring activation for sequence-specific DNA binding.

MeSH Terms (12)

Active Transport, Cell Nucleus Binding Sites Cell Nucleus Computer Simulation Diffusion DNA DNA-Binding Proteins Kinetics Models, Biological Models, Chemical Protein Binding Tumor Suppressor Protein p53

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