Downregulation of the cdc2/cyclin B protein kinase activity by binding of p53 to p34(cdc2).
We previously found that p53 binds to the catalytic subunit of the p34(cdc2)/cyclin B1-kinase. In the present study we analyzed the functional consequences of this interaction. Binding of wild-type p53 to p34(cdc2)/cyclin B1 results in a significant decrease of its histone H1 kinase activity. Binding of p53 to the kinase is a prerequisite for the inhibition because a mutant p53 which lacks the binding region fails to influence the enzymatic activity. Furthermore, by using C-terminal fragments of p53 it became obvious that also some other structural elements in the N-terminal region are necessary for the inhibitory effect. Our present study provides evidence that p53 might regulate cell-cycle checkpoints not only on the transcriptional level but also by binding to the cell-cycle regulating kinase p34(cdc2).
Ababneh
M
M
Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Gebäude 44, Homburg, 66421, Germany.
Götz
C
C
Montenarh
M
M
D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D015536:Down-Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase