p53 Linear Diffusion along DNA Requires Its C Terminus

• Published in: Molecular cell 2004-11, Vol.16 (3), p.413-424
• Main Authors: McKinney, Kristine, Mattia, Melissa, Gottifredi, Vanesa, Prives, Carol
• Format: Article
• Language: English
• Subjects: Acetylation; Chromatin Immunoprecipitation; DNA - chemistry; DNA - metabolism; Electrophoretic Mobility Shift Assay; Gene Expression Regulation; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Mutation; Phosphorylation; Promoter Regions, Genetic - genetics; Transcriptional Activation - genetics; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2004.09.032

In cells, sequence-specific transcription factors must search through an entire genome to find their target sites in promoters. Such sites may be identified by using one-dimensional (linear diffusion) and/or three-dimensional (association/dissociation) mechanisms. We show here that wild-type p53 possesses the ability to linearly diffuse on DNA. p53 lacking its C terminus is incapable of such sliding along DNA, while the isolated C terminus of p53 is even more effective than the full-length protein at one-dimensional linear diffusion. Importantly, neither acetylation-mimicking mutations nor phosphorylation of residues within the C terminus stimulates linear diffusion by p53. Supporting these in vitro observations, we found that C-terminally deleted p53 (p53Δ30) expressed at physiological levels is deficient in binding to and transactivating downstream promoters in vivo. Therefore, our data show that the C terminus is a positive regulator of DNA binding in vivo and in vitro, and indicate that the mechanism may involve linear diffusion.