Publication Date:
2000-03-04
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winkler, K E -- Swenson, K I -- Kornbluth, S -- Means, A R -- CA 82845/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1644-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698738" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aphidicolin/pharmacology
;
Cell Cycle
;
*Cell Cycle Proteins
;
Cyclin B/metabolism
;
*DNA Replication
;
Enzyme Inhibitors/pharmacology
;
G2 Phase
;
*Mitosis
;
*Nuclear Proteins
;
Nucleic Acid Synthesis Inhibitors
;
Oocytes
;
Peptidylprolyl Isomerase/genetics/*metabolism/pharmacology
;
Point Mutation
;
Protein Kinases/metabolism
;
Protein-Serine-Threonine Kinases/metabolism
;
Protein-Tyrosine Kinases/metabolism
;
Recombinant Proteins/metabolism/pharmacology
;
*Xenopus Proteins
;
Xenopus laevis
;
cdc25 Phosphatases/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
