Elucidating cdc25's Oncogenic Mechanism in Breast Cancer Using Pin1, a Negative Mitotic Regulator
Abstract
The peptidyl-prolyl isomerase Pin1 has been implicated in regulating cell cycle progression. Pin 1 was found to be required for the DNA replication checkpoint in Xenopus laevis. Egg extracts depleted of Pin1 inappropriately transited from G2 to M phase of the cell cycle in the presence of the DNA replication inhibitor aphidicolin. This defect in replication checkpoint function was reversed after addition of recombinant wild type Pin 1, 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 MPM-2 epitopes. Therefore, Pin 1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB266029
Entities
People
- Anthony Means
- Katharine Winkler
Organizations
- Duke University Hospital