TY - JOUR
T1 - When the checkpoints have gone
T2 - insights into Cdc25 functional activation.
AU - Margolis, Seth S.
AU - Kornbluth, Sally
N1 - Copyright:
MEDLINE® is the source for the citation and abstract of this record.
PY - 2004/4
Y1 - 2004/4
N2 - DNA-responsive checkpoints operate at the G(2)/M transition to prevent premature mitosis in the presence of incompletely replicated or damaged DNA. These pathways prevent mitotic entry, at least in part, by suppressing Cdc25, the phosphatase that activates Cdc2/Cyclin B. To gain insight into how checkpoint signaling controls Cdc25 function, we have carefully examined the individual steps in Cdc25 activation. We found that removal of the regulatory protein, 14-3-3, that binds to phosphorylated Cdc25 during interphase is one of the early steps in mitotic activation. Moreover, our studies unexpectedly implicated the phosphatase PP1 and the G(1)/S kinase Cdk2 in the process of Cdc25 activation. Here we integrate our findings and those of others to propose a model for Cdc25 activation in an effort to provide insight into novel loci of DNA-responsive checkpoint control of mitotic entry.
AB - DNA-responsive checkpoints operate at the G(2)/M transition to prevent premature mitosis in the presence of incompletely replicated or damaged DNA. These pathways prevent mitotic entry, at least in part, by suppressing Cdc25, the phosphatase that activates Cdc2/Cyclin B. To gain insight into how checkpoint signaling controls Cdc25 function, we have carefully examined the individual steps in Cdc25 activation. We found that removal of the regulatory protein, 14-3-3, that binds to phosphorylated Cdc25 during interphase is one of the early steps in mitotic activation. Moreover, our studies unexpectedly implicated the phosphatase PP1 and the G(1)/S kinase Cdk2 in the process of Cdc25 activation. Here we integrate our findings and those of others to propose a model for Cdc25 activation in an effort to provide insight into novel loci of DNA-responsive checkpoint control of mitotic entry.
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M3 - Article
C2 - 15020839
AN - SCOPUS:4644262376
SN - 1538-4101
VL - 3
SP - 425
EP - 428
JO - Cell cycle (Georgetown, Tex.)
JF - Cell cycle (Georgetown, Tex.)
IS - 4
ER -