Requirement of the prolyl isomerase Pin1 for the replication checkpoint.
The peptidyl-prolyl isomerase Pin1 has been implicated in regulating cell cycle progression. Pin1 was found to be required for the DNA replication checkpoint in Xenopus laevis. Egg extracts depleted of Pin1 inappropriately transited from the G2 to the M phase of the cell cycle in the presence of the DNA replication inhibitor aphidicolin. This defect in replication checkpoint function was reversed after the addition of recombinant wild-type Pin1, but not an isomerase-inactive mutant, to the depleted extract. Premature mitotic entry in the absence of Pin1 was accompanied by hyperphosphorylation of Cdc25, activation of Cdc2/cyclin B, and generation of epitopes recognized by the mitotic phosphoprotein antibody, MPM-2. Therefore, Pin1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.
Winkler
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Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA.
Swenson
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Kornbluth
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Means
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D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000378:metabolism; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016195:G2 Phase; D008938:Mitosis; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D009865:Oocytes; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017354:Point Mutation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis; D020687:cdc25 Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D016590:Aphidicolin; D011494:Protein Kinases; C095970:MYT1 kinase, Xenopus; C530005:WEE1 protein, Xenopus; C102333:histone H1 kinase; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D020687:cdc25 Phosphatases; D019696:Peptidylprolyl Isomerase