Regulation of the specific DNA binding function of p53

Cell. 1992 Nov 27;71(5):875-86. doi: 10.1016/0092-8674(92)90562-q.


The DNA binding activity of p53 is required for its tumor suppressor function; we show here that this activity is cryptic but can be activated by cellular factors acting on a C-terminal regulatory domain of p53. A gel mobility shift assay demonstrated that recombinant wild-type human p53 binds DNA sequence specifically only weakly, but a monoclonal antibody binding near the C terminus activated the cryptic DNA binding activity stoichiometrically. p53 DNA binding could be activated by a C-terminal deletion of p53, mild proteolysis of full-length p53, E. coli dnaK (which disrupts protein-protein complexes), or casein kinase II (and coincident phosphorylation of a C-terminal site on p53). Activation of p53 DNA binding may be critical in regulation of its ability to arrest cell growth and thus its tumor suppressor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Reactions
  • Base Sequence
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Casein Kinases
  • Cells, Cultured
  • Heat-Shock Proteins / metabolism
  • In Vitro Techniques
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism
  • Protein Kinases / metabolism
  • Rats
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Trypsin / pharmacology
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Suppressor Protein p53 / metabolism*


  • Carrier Proteins
  • Heat-Shock Proteins
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Protein Kinases
  • Casein Kinases
  • Trypsin