Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases

T R Hupp, D P Lane

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

p53 is an allosterically regulated protein with a latent DNA-binding activity. Posttranslational modification of a carboxy-terminal regulatory site in vitro, by casein kinase II and protein kinase C, can activate the sequence-specific DNA-binding function of the wild-type protein. The latent form of p53 is produced in a variety of eukaryotic and prokaryotic cell lines, including E. coli, Sf9 insect cells, and C6 cells, indicating that the activation of p53 in vivo is rate-limiting. In addition, phosphorylation of p53 at the protein kinase C site and activation in vivo correlate with the loss of reactivity of active p53 protein to the carboxy-terminal antibody, PAb421. These results suggest that two highly conserved protein kinases modify polypeptide structure through a common biochemical mechanism and that different enzymatic pathways may channel information into the carboxy-terminal regulatory site of p53, allosterically activating its function as a tumor suppressor.
Original languageEnglish
Pages (from-to)195-206
Number of pages12
JournalCold Spring Harbor Symposia on Quantitative Biology
Volume59
Publication statusPublished - 1994

Keywords / Materials (for Non-textual outputs)

  • Allosteric Site
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Binding Sites
  • Casein Kinase II
  • Cell Line
  • DNA
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinase C
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Tumor Suppressor Protein p53

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