C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity

Nucleic Acids Res. 2008 Apr;36(6):1900-12. doi: 10.1093/nar/gkn044. Epub 2008 Feb 11.


The p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA-binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity: while p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, target gene activation and induction of cell cycle arrest or apoptosis. A basic CTD therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. The different DNA-binding characteristics of the p53 family members could therefore reflect their predominant role in the cellular stress response (p53) or developmental processes (p73).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Binding Sites
  • Cell Cycle
  • Cell Line
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Diffusion
  • Humans
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Transcription, Genetic
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / chemistry*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA