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Cdc25

About: Cdc25 is a(n) research topic. Over the lifetime, 727 publication(s) have been published within this topic receiving 58224 citation(s). The topic is also known as: Cdc25 phosphatase.
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Journal ArticleDOI
05 Apr 2001-Oncogene
TL;DR: Evidence that implicates p53 in controlling entry into mitosis when cells enter G2 with damaged DNA or when they are arrested in S phase due to depletion of the substrates required for DNA synthesis is reviewed.
Abstract: p53 protects mammals from neoplasia by inducing apoptosis, DNA repair and cell cycle arrest in response to a variety of stresses. p53-dependent arrest of cells in the G1 phase of the cell cycle is an important component of the cellular response to stress. Here we review recent evidence that implicates p53 in controlling entry into mitosis when cells enter G2 with damaged DNA or when they are arrested in S phase due to depletion of the substrates required for DNA synthesis. Part of the mechanism by which p53 blocks cells at the G2 checkpoint involves inhibition of Cdc2, the cyclin-dependent kinase required to enter mitosis. Cdc2 is inhibited simultaneously by three transcriptional targets of p53, Gadd45, p21, and 14-3-3σ. Binding of Cdc2 to Cyclin B1 is required for its activity, and repression of the cyclin B1 gene by p53 also contributes to blocking entry into mitosis. p53 also represses the cdc2 gene, to help ensure that cells do not escape the initial block. Genotoxic stress also activates p53-independent pathways that inhibit Cdc2 activity, activation of the protein kinases Chk1 and Chk2 by the protein kinases Atm and Atr. Chk1 and Chk2 inhibit Cdc2 by inactivating Cdc25, the phosphatase that normally activates Cdc2. Chk1, Chk2, Atm and Atr also contribute to the activation of p53 in response to genotoxic stress and therefore play multiple roles. p53 induces transcription of the reprimo, B99, and mcg10 genes, all of which contribute to the arrest of cells in G2, but the mechanisms of cell cycle arrest by these genes is not known. Repression of the topoisomerase II gene by p53 helps to block entry into mitosis and strengthens the G2 arrest. In summary, multiple overlapping p53-dependent and p53-independent pathways regulate the G2/M transition in response to genotoxic stress.

1,434 citations


Journal ArticleDOI
05 Sep 1997-Science
TL;DR: Results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify CDC25C as a potential target of checkpoint control in human cells.
Abstract: Human Cdc25C is a dual-specificity protein phosphatase that controls entry into mitosis by dephosphorylating the protein kinase Cdc2. Throughout interphase, but not in mitosis, Cdc25C was phosphorylated on serine-216 and bound to members of the highly conserved and ubiquitously expressed family of 14-3-3 proteins. A mutation preventing phosphorylation of serine-216 abrogated 14-3-3 binding. Conditional overexpression of this mutant perturbed mitotic timing and allowed cells to escape the G2 checkpoint arrest induced by either unreplicated DNA or radiation-induced damage. Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-216. These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells.

1,407 citations


Journal ArticleDOI
05 Sep 1997-Science
TL;DR: Results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry.
Abstract: In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng et al. in this issue, serine-216 phosphorylation creates a binding site for 14-3-3 protein and inhibits function of the phosphatase. These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry.

1,350 citations


Journal ArticleDOI
Paul Russell1, Paul Nurse1
22 May 1987-Cell
TL;DR: Fission yeast wee1- mutants initiate mitosis at half the cell size of wild type and functions as a dose-dependent inhibitor of mitosis, the first such element to be specifically identified and cloned.
Abstract: Fission yeast wee1 − mutants initiate mitosis at half the cell size of wild type. The wee1 + activity is required to prevent lethal premature mitosis in cells that overproduce the mitotic inducer cdc25 + . This lethal phenotype was used to clone wee1 + by complementation. When wee1 + expression is increased, mitosis is delayed until cells grow to a larger size. Thus wee1 + functions as a dose-dependent inhibitor of mitosis, the first such element to be specifically identified and cloned. The carboxy-terminal region of the predicted 112 kd wee1 + protein contains protein kinase consensus sequences, suggesting that negative regulation of mitosis involves protein phosphorylation. Genetic evidence indicates that wee1 + and cdc25 + compete in a control system regulating the cdc2 + protein kinase, which is required for mitotic initiation.

921 citations


Journal ArticleDOI
Paul Russell1, Paul Nurse1
11 Apr 1986-Cell
TL;DR: Evidence is described showing that cdc25+ functions to counteract the activity of the mitotic inhibitor wee1+, and indicating that both mitotic control elements act independently to regulate the initiation of mitosis.
Abstract: In the fission yeast S. pombe the cdc25+ gene function is required to initiate mitosis. We have cloned the cdc25+ gene and have found that increased cdc25+ expression causes mitosis to initiate at a reduced cell size. This shows that cdc25+ functions as a dosage-dependent inducer in mitotic control, the first such mitotic control element to be specifically identified. DNA sequencing of the cdc25+ gene has shown that it can encode a protein of MW 67,000. Evidence is described showing that cdc25+ functions to counteract the activity of the mitotic inhibitor wee1+, and indicating that both mitotic control elements act independently to regulate the initiation of mitosis.

916 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20219
20209
201912
20189
201718
201620

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Topic's top 5 most impactful authors

Bernard Ducommun

28 papers, 2K citations

Paul Russell

17 papers, 2.1K citations

Peter Wipf

13 papers, 840 citations

David Beach

9 papers, 1.8K citations

Gregoire Prevost

8 papers, 153 citations