The DNA binding activity of p53 displays reaction-diffusion kinetics. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • April 7, 2006

Research

keywords

  • Cell Nucleus
  • DNA
  • Models, Biological
  • Tumor Suppressor Protein p53

Identity

PubMed Central ID

  • PMC1479054

Scopus Document Identifier

  • 33745747107

Digital Object Identifier (DOI)

  • 10.1529/biophysj.105.078303

PubMed ID

  • 16603489

Additional Document Info

volume

  • 91

issue

  • 1