Abstract
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 language | English |
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Pages (from-to) | 195-206 |
Number of pages | 12 |
Journal | Cold Spring Harbor Symposia on Quantitative Biology |
Volume | 59 |
Publication status | Published - 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