Interference between p53 and cdc25C in cell cycle regulation.
The eukaryotic cell cycle is regulated by a network of different protein kinases and phosphatases which are by various mechanisms linked to the growth suppressor p53. Cell cycle regulation is quite similar from yeast to man. Although there is no endogenous p53 in yeast expression of human p53 led to growth arrest of yeast cells which can be suppressed by simultaneous overexpression of cdc25C, a phosphatase regulating entry into mitosis. Herein, we show that overexpression of cdc25C in mammalian cells is insufficient in suppressing a p53 induced growth arrest. We further show that p53 is co-immunoprecipitated with cdc25C and p53 inhibits the cdc25C phosphatase activity in a dose-dependent manner. Thus, our data show that p53 like other binding partners of cdc25C, regulates entry into mitosis by binding to cdc25C.
Ruppenthal
Sandra L
SL
Medical Biochemistry and Molecular Biology, University of the Saarland, D-66424 Homburg, Germany.
Noll
Andreas
A
Götz
Claudia
C
Montenarh
Mathias
M
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D010744:Phosphoric Monoester Hydrolases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases