Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein.
We report here that the negative cell cycle regulator protein p53 is an in vivo and in vitro substrate for protein kinase C, a cellular receptor for the tumor-promoter phorbol esters. We also demonstrate that p53 interacts in a calcium-dependent manner with S100b, a member of the S100 protein family involved in cell cycle progression and cell differentiation, and that such an interaction inhibits in vitro p53 phosphorylation by protein kinase C. The interaction between p53 and S100b was utilized for the purification of cellular and recombinant murine p53 by affinity chromatography with S100b-Sepharose. Furthermore, and of particular interest, we have shown that purified p53 undergoes temperature-dependent oligomerization and that the interaction between S100b and p53 not only induces total inhibition of p53 oligomerization but also promotes disassembly of the p53 oligomers. We suggest that these effects result from the binding of S100b to the multifunctional basic C-terminal domain of p53 and propose that p53 may be a cellular target for the S100 protein family members involved in the control of the cell cycle at the G0-G1/S boundary.
Baudier
J
J
Laboratoire de Biologie Moléculaire du Cycle Cellulaire, Institut National de la Santé et de la Recherche Médicale Unité 309, Grenoble, France.
Delphin
C
C
Grunwald
D
D
Khochbin
S
S
Lawrence
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002147:Calmodulin; D046911:Macromolecular Substances; D010750:Phosphoproteins; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D011493:Protein Kinase C