Cell cycle regulation by the Cdc25 phosphatase family

Nilsson, Ida; Hoffmann, Ingrid

doi:10.1007/978-1-4615-4253-7_10

Cited by 409 publications

(329 citation statements)

References 69 publications

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“…The family of Cdc25 dualspecificity phosphatases controls the cell cycle at different phases. [5][6][7] Cdc25A was shown to regulate G1-S transition by dephosphorylating threonine 14 and tyrosine 15 of cyclindependent kinase 2 (Cdk2), [8][9][10][11][12][13] and by competition with p21 for cyclinA/Cdk2 and cylinE/Cdk2 binding sites. 14 Moreover, Cdc25A degradation is part of a DNA-damage checkpoint mechanism.…”

Section: Introductionmentioning

confidence: 99%

Subcellular localisation of Cdc25A determines cell fate

et al. 2003

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Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKBprotein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.

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Section: Introductionmentioning

confidence: 99%

Subcellular localisation of Cdc25A determines cell fate

et al. 2003

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“…promoting cyclin E2 and the Cdc25C phosphatase (Table 1; Figure 3), the latter of which activates Cdk1 during cellular progression into M-phase (Nilsson and Hoffmann, 2000). Persistent pulmonary inflammation in Rosa26-Foxm1 lungs was associated with increased expression of Lipocalin-2, the CXC chemokine ligand 5 (CXCL5), CXCL1, and the CC chemokine ligand 3 (CCL3) (Figure 3), all of which stimulate signaling pathways essential for pulmonary inflammation and lung remodeling (Bratt, 2000;Kulbe et al, 2004).…”

Section: Foxm1 Induces Formation Of Lung Tumors I-c Wang Et Almentioning

confidence: 99%

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

et al. 2008

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The forkhead box m1 (Foxm1 or Foxm1b) protein (previously called HFH-11B, Trident, Win or MPP2) is abundantly expressed in human non-small cell lung cancers where it transcriptionally induces expression of genes essential for proliferation of tumor cells. In this study, we used Rosa26-Foxm1 transgenic mice, in which the Rosa26 promoter drives ubiquitous expression of Foxm1 transgene, to identify new signaling pathways regulated by Foxm1. Lung tumors were induced in Rosa26-Foxm1 mice using the 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT) lung tumor initiation/promotion protocol. Tumors from MCA/BHTtreated Rosa26-Foxm1 mice displayed a significant increase in the number, size and DNA replication compared to wild-type mice. Elevated tumor formation in Rosa26-Foxm1 transgenic lungs was associated with persistent pulmonary inflammation, macrophage infiltration and increased expression of cyclooxygenase-2 (Cox-2), Cdc25C phosphatase, cyclin E2, chemokine ligands CXCL5, CXCL1 and CCL3, cathepsins and matrix metalloprotease-12. Cell culture experiments with A549 human lung adenocarcinoma cells demonstrated that depletion of Foxm1 by either short interfering RNA transfection or treatment with Foxm1-inhibiting ARF 26-44 peptide significantly reduced Cox-2 expression. In co-transfection experiments, Foxm1 protein-induced Cox-2 promoter activity and directly bound to the À2566/ À2580 bp region of human Cox-2 promoter.

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“…The DSP subclass is now emerging as an important group of regulators of cell cycle control and mitogenic signal transduction (Keyse, 1995;Denu et al, 1996;Galaktionov et al, 1996;Maehema and Dixon, 1998). Among them, Cdc25 protein phosphatases are believed to be important regulators in control of cell cycle progression by activating cyclin-dependent kinases (Cdk) (Nilsson and Hoffman, 2000). Three Cdc25 homologs have been found in mammals, Cdc25A, Cdc25B, and Cdc25C (Sadhu et al, 1990;Millar et al, 1991;Nagata et al, 1991).…”

Section: Mechanisms Of Cell Growth Inhibition By K Vitamin Analogs Prmentioning

confidence: 99%

K vitamins, PTP antagonism, and cell growth arrest

Carr

Wang

Kar

2002

Journal Cellular Physiology

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The main function of K vitamins is to act as co-factors for g-glutamyl carboxylase. However, they have also recently been shown to inhibit cell growth. We have chemically synthesized a series of K vitamin analogs with various side chains at the 2 or 3 position of the core naphthoquinone structure. The analogs with short thio-ethanol side chains are found to be more potent growth inhibitors in vitro of various tumor cell lines. Cpd 5 or [2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone] is one of the most potent. The anti-proliferation activity of these compounds is antagonized by exogenous thiols but not by non-thiol antioxidants. This suggests that the growth inhibition is mediated by sulfhydryl arylation of cellular glutathione and cysteine-containing proteins and not by oxidative stress. The protein tyrosine phosphatases (PTP) are an important group of proteins that contain cysteine at their catalytic site. PTPs regulate mitogenic signal transduction and cell cycle progression. PTP inhibition by Cpd 5 results in prolonged tyrosine phosphorylation and activation of several kinases and transcription factors including EGFR, ERK1/2, and Elk1. Cpd 5 could activate ERK1/2 either by signaling from an activated EGFR, which is upstream in the signaling cascade, or by direct inhibition of ERK1/2 phosphatase(s). Prolonged ERK1/2 phosphorylation strongly correlates with Cpd 5-mediated growth inhibition. Cpd 5 can also bind to and inhibit the Cdc25 family of dual specific phosphatases. As a result, several Cdc25 substrates (Cdk1, Cdk2, Cdk4) involved in cell cycle progression are tyrosine phosphorylated and thereby inhibited by its action. Cpd 5 could also inhibit both normal liver regeneration and hepatoma growth in vivo. DNA synthesis during rat liver regeneration following partial hepatectomy, transplantable rat hepatoma cell growth, and glutathione-S-transferase-pi expressing hepatocytes after administration of the chemical carcinogen diethylnitrosamine, are all inhibited by Cpd 5 administration. The growth inhibitory effect during liver regeneration and transplantable tumor growth is also correlated with ERK1/2 phosphorylation induced by Cpd 5. Thus, Cpd 5-mediated inhibition of PTPs, such as Cdc25 leads to cell growth arrest due to altered activity of key cellular kinases involved in signal transduction and cell cycle progression. This prototype K vitamin analog represents a novel class of growth inhibitor based upon its action as a selective PTP antagonist. It is clearly associated with prolonged ERK1/2 phosphorylation, which is in contrast with the transient ERK1/2 phosphorylation induced by growth stimulatory mitogens.

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Cell cycle regulation by the Cdc25 phosphatase family

Cited by 409 publications

References 69 publications

Subcellular localisation of Cdc25A determines cell fate

Subcellular localisation of Cdc25A determines cell fate

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

K vitamins, PTP antagonism, and cell growth arrest

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