Binding of the growth suppressor p53 protein to the cell cycle regulator phosphatase cdc25C.
Human p53 is a growth suppressor which not only functions in mammalian cells but also in fission yeast. It was previously shown that the cell cycle regulating phosphatase cdc25C suppresses the p53 induced growth arrest in fission yeast. In the present study we analysed the mechanism of this suppression. We found that cdc25C directly interacts with p53. By using different deletion mutants the binding region was narrowed down on the polypeptide chain of p53 to amino acids 287-340. To test the functional significance we analysed the effect of this interaction on the DNA binding activity of p53. As shown by band shift experiments binding of cdc25C to p53 does not modify the DNA binding activity of p53. Our data suggest that the observed suppression of the p53 induced growth arrest by cdc25C might be achieved by direct binding of cdc25C to the C-terminus of p53.
Rief
N
N
Medical Biochemistry and Molecular Biology, University of the Saarland, D-66421 Homburg, Germany.
Herges
H
H
Prowald
A
A
Götz
C
C
Montenarh
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases