Casein kinase II and the tumor suppressor protein P53 associate in a molecular complex that is negatively regulated upon P53 phosphorylation.
Selective immunoisolation of P53 from Sf9 cells coexpressing wild-type P53 and casein kinase II yielded a preparation containing casein kinase II, thus suggesting that the two proteins may associate in a molecular complex in the intact cell. Such a complex could indeed be demonstrated in vitro between purified recombinant P53 and oligomeric casein kinase II and was shown to dissociate when P53 became phosphorylated by the kinase. This suggested that the P53 C-terminal domain, which contains the casein kinase II phosphorylation site was involved in the protein-protein interaction; this was confirmed by the fact that an anti-P53 monoclonal antibody directed to that domain inhibited the P53-casein kinase II association. Studies with isolated recombinant casein kinase II subunits disclosed that although the alpha (catalytic) subunit could phosphorylate P53, the formation of a stable P53-casein kinase II association required the presence of the beta subunit of the kinase. This was confirmed by immunoisolation of a P53-beta subunit complex from cells expressing both polypeptides. Although the biological significance of a reversible P53-casein kinase II molecular complex in the control of cell proliferation processes remains to be defined, these observations suggest the possibility of a novel mechanism regulating P53 and casein kinase II activities in the intact cell.
Filhol
O
O
Institut National de la Santé et de la Recherche Médicale Unité 244, Biochimie de Régulations Cellulaires et Endocrines, Grenoble, France.
Baudier
J
J
Delphin
C
C
Loue-Mackenbach
P
P
Chambaz
E M
EM
Cochet
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D047390:Casein Kinase II; D002460:Cell Line; D006706:Homeostasis; D007313:Insecta; D007700:Kinetics; D046911:Macromolecular Substances; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D010761:Phosphorus Radioisotopes; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D013096:Spermine; D000255:Adenosine Triphosphate; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases