The when and wheres of CDC25 phosphatases

Boutros, Rose; Dozier, Christine; Ducommun, Bernard

doi:10.1016/j.ceb.2006.02.003

Cited by 375 publications

(327 citation statements)

References 69 publications

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“…This regulation is associated with increased expression of the active dephosphorylated forms of the phosphatases. Elevated expression of Cdc25A and B has been described in several malignancies (Boutros et al, 2006), including human carcinomas of the breast and lung tumors. In colorectal cancer patients, overexpression of Cdc25B protein phosphatase is a marker of poor prognosis (Takemasa et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…In colorectal cancer patients, overexpression of Cdc25B protein phosphatase is a marker of poor prognosis (Takemasa et al, 2000). The nuclear phosphatases Cdc25A and B are potential oncogenic proteins associated with cell proliferation, foci formation, hypergrowth activity, and control of the G2/M checkpoint in response to DNA damage (Galaktionov et al, 1995;Daga and Jimenez, 1999;Xu et al, 2003;Boutros et al, 2006). The biological rationale of our results is further sustained by the induction of TFF1 in inflammatory hyperplastic polyps, premalignant and early stages of colon cancer, as shown here by RT-PCR, immunohistochemistry, and previously by immunoblot analysis (Emami et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In PC/AA/C1-TFF1 cells, transcripts levels of Cdc25a, b and c were not increased as compared to parental PC/AA/C1 cells (not shown), indicating that Cdc25s are also post-transcriptionnaly regulated by TFF1. For example, Cdc25A protein has a short half-life, is regulated in a cell cycle-dependent manner by nuclear import/ export, subcellular localization, 14-3-3 binding and cytoplasmic sequestration, and b-TrCP/proteasome-mediated degradation (Boutros et al, 2006). In breast cancer patients, the abundance of Cdc25A is mainly the result of increased stability rather than increased transcript accumulation (Lo¨ffler et al, 2003).…”

Section: Tff1 Transforming Functions and Cdc25 Phosphatases S Rodrigumentioning

confidence: 99%

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Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Tff1 Transforming Functions and Cdc25 Phosphatases S Rodrigumentioning

confidence: 99%

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Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

et al. 2006

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“…At G2, Chk1 is activated by ATR to phosphorylate CDC25A, -B, and -C (Boutros, 2006), preventing cyclin B/CDK1 activation and resulting in G2 arrest. Another mechanism of G2 arrest is provided by stress-induced activation of p38 MAPK/MK2 and subsequent inactivation of CDC25B/C, as described earlier (Manke et al, 2005;Reinhardt et al, 2007).…”

Section: G2 Checkpointmentioning

confidence: 99%

G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer

2008

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Rigorous quality control steps, termed checkpoints, tightly regulate progression through the cell cycle. DNA-damaging chemotherapy and radiation activate functional cellular checkpoints. These checkpoints can facilitate DNA repair and promote cell death in unrepaired cells. There are at least three DNA damage checkpoints -at G1/S, S, and G2/M -as well as a mitotic spindle checkpoint. Most cancer cells harbour mutations in tumour suppressors and/or oncogenes, which impair certain cell checkpoints. Inhibiting the remaining cell checkpoints -particularly after exposure of cancer cells to chemotherapy and/or radiation -allows cell death, a strategy now being employed in cancer therapeutics. With our increasing knowledge of cell cycle regulation, many compounds have been developed to inhibit specific checkpoint components, particularly at the G2/M transition. One such target is checkpoint kinase-1 (Chk1). We review here the molecular framework of the cell cycle, the rationale for targeting Chk1, the preclinical concepts related to the development of Chk1 inhibitors, and the efficacy and safety results from Chk1 inhibitors now in phase I/II trials. British Journal of Cancer (2008) The cell cycle is organised into a series of dependent pathways, whereby the initiation of each event is dependent upon successful completion of previous events. In this way, replicating cells traverse the four distinct phases of the cell cycle consecutively: G1 followed by S, followed by G2 and, finally, M. This ordered progression is guarded by checkpoints capable of delaying the cell cycle in response to intra-or extracellular stressors. As part of the cell cycle surveillance system, the DNA damage and spindle checkpoints protect the cell from genomic instability. Checkpoints are important quality control measures that ensure the proper sequence of cell cycle events and allow cells to respond to DNA damage.Increasingly, checkpoint inhibition has become an area of novel drug development. In the setting of DNA damage, checkpoint inhibition leads to genomic instability, and subsequent cell death. The first checkpoint, found at the G1/S transition, is compromised in many malignant cells, due to mutations in various tumour suppressor genes, including retinoblastoma protein (Rb) and p53. Cells deficient in the G1 checkpoint are dependent on the S and G2 checkpoints for DNA repair. Checkpoint kinase-1 (Chk1) is an active transducer kinase at both the S and G2 checkpoints, rendering it a target for rational anticancer drug development. In the presence of DNA damage, Chk1 inactivation abrogates G2 arrest, resulting in preferential cancer cell death .This article serves to review the (1) current molecular pathways comprising the cell cycle checkpoint machinery, (2) inhibition of Chk1 as an effective means of abrogating G2 arrest, and (3) current Chk1 inhibitors in use in phase I clinical trials.

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“…While using mouse oocytes, Han et al demonstrated that mouse Wee1B was involved in the maintenance of meiotic arrest through PKAmediated phosphorylation (Han et al, 2005). Because the presence of ubiquitous and highly conserved Cdc25 and Wee1 kinase family has been well established from yeast to mammals (Parker and Piwnica-Worms, 1992;Nakanishi et al, 2000;Nilsson and Hoffmann, 2000;Boutros et al, 2006), the above findings led to a hypothesis that may explain the cAMP and PKA inhibitory effects on MPF activity, that is, PKA directly phosphorylates and regulates the activity of the Cdc25 phosphatase and Wee1/Myt1 kinase, which then directly determines the phosphorylation state of the MPF complex and meiotic resumption.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

Zhang

et al. 2008

Developmental Dynamics

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Protein kinase A (PKA) play a critical role in maintaining the meiotic arrest. However, the steps downstream of PKA remain largely unknown. In this study, we investigated the regulation of meiotic resumption by PKA/Cdc25B pathway in mouse oocytes. Injection of mRNA coding for Cdc25b-S321A had a more potent maturation-inducing ability than Cdc25b-WT. When co-injected with PKA inhibitor, Cdc25B-WT had similar activities with Cdc25B-S321A. Meanwhile, the phosphorylation of Cdc25B-S321 was detected in germinal vesicle (GV) oocytes by Western blotting with a phospho-Ser321-specific antibody and the band disappeared when oocytes reenter into the meiotic cell cycle. Furthermore, Cdc25B-WT translocated to the nucleus shortly before GV breakdown (GVBD), whereas phosphorylated Cdc25B-S321 expressed exclusively in the cytoplasm and the signal could not be detected in GVBD oocytes. Taken together, these data indicate that Cdc25B-Serine321 is the potential PKA target and Cdc25B subcellular localization determines its function during the process of maintaining GV arrest in mouse oocytes. Developmental Dynamics 237: 3777-3786, 2008.

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The when and wheres of CDC25 phosphatases

Cited by 375 publications

References 69 publications

Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

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