The Cell Cycle-Regulatory CDC25A Phosphatase Inhibits Apoptosis Signal-Regulating Kinase 1

Zou, Xinying; Tsutsui, Tateki; Ray, Dipankar; Blomquist, James F.; Ichijo, Hidenori; Ucker, David S.; Kiyokawa, Hiroaki

doi:10.1128/mcb.21.14.4818-4828.2001

Cited by 91 publications

(75 citation statements)

References 68 publications

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“…18 Another report demonstrated that Cdc25A inhibited cytoplasmic ASK1 independent of its phosphatase activity, thereby blocking cell death triggered by oxidative stress. 19 Hence, we fused the cDNA of Cdc25A to that of ER, which allows for Tamoxifen (4-OHT)-mediated shuttle of the Cdc25A:ER protein from the cytoplasm into the nucleus. The results from this investigation suggested that Cdc25A protected from apoptosis only when it was localised in the cytoplasm, because upon 4-OHT treatment, the cytoplasmic Cdc25A:ER level diminished and increased in the nuclei of rat 423 cells within 2 h, followed by degradation within 8 h. Hence, the loss of antiapoptotic function of Cdc25A:ER correlated with the decreased cytoplasmic expression upon exposure to 4-OHT.…”

Section: Discussionmentioning

confidence: 99%

“…However, Cdc25A also interacts with Raf1 by virtue of 14.3.3 proteins [16][17][18] and apoptosis signalregulating kinase (ASK)1. 19 This, in contrast, points to a cytoplasmic function of Cdc25A. It was demonstrated recently that in rat 423 cells the bulk of Cdc25A was actually localised in the cytoplasm and that apoptosis was inhibited by Cdc25A due to the PKB-protein kinase B (Akt) survival pathway activation.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Subcellular localisation of Cdc25A determines cell fate

et al. 2003

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“…Furthermore, Cdc25A, which is involved in the control of the G 1 /S transition, binds to a region adjacent to the ASK1 kinase domain and inhibits the kinase activity of ASK1 in a manner independent of the phosphatase activity. 47 As Cdc25A and Cdc25C proteins function in different stages of the cell cycle, 2,3,5 ASK1 might be regulated in several stages of the cell cycle. There are several pieces of evidence that ASK1 phosphorylation is cell cycle dependent.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1

Cho

Park

et al. 2015

Cell Death Differ

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Cdc25C (cell division cycle 25C) phosphatase triggers entry into mitosis in the cell cycle by dephosphorylating cyclin B-Cdk1. Cdc25C exhibits basal phosphatase activity during interphase and then becomes activated at the G 2 /M transition after hyperphosphorylation on multiple sites and dissociation from 14-3-3. Although the role of Cdc25C in mitosis has been extensively studied, its function in interphase remains elusive. Here, we show that during interphase Cdc25C suppresses apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein (MAP) kinase kinase kinase family that mediates apoptosis. Cdc25C phosphatase dephosphorylates phospho-Thr-838 in the activation loop of ASK1 in vitro and in interphase cells. In addition, knockdown of Cdc25C increases the activity of ASK1 and ASK1 downstream targets in interphase cells, and overexpression of Cdc25C inhibits ASK1-mediated apoptosis, suggesting that Cdc25C binds to and negatively regulates ASK1. Furthermore, we showed that ASK1 kinase activity correlated with Cdc25C activation during mitotic arrest and enhanced ASK1 activity in the presence of activated Cdc25C resulted from the weak association between ASK1 and Cdc25C. In cells synchronized in mitosis following nocodazole treatment, phosphorylation of Thr-838 in the activation loop of ASK1 increased. Compared with hypophosphorylated Cdc25C, which exhibited basal phosphatase activity in interphase, hyperphosphorylated Cdc25C exhibited enhanced phosphatase activity during mitotic arrest, but had significantly reduced affinity to ASK1, suggesting that enhanced ASK1 activity in mitosis was due to reduced binding of hyperphosphorylated Cdc25C to ASK1. These findings suggest that Cdc25C negatively regulates proapoptotic ASK1 in a cell cycle-dependent manner and may play a role in G 2 /M checkpointmediated apoptosis.

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“…However, oxidative stress causes dissociation of the Trx-ASK1 complex leading to activation of JNK and p38. CDC25A, a phosphatase that promotes cell cycle progression also binds to and inhibits ASK1 activity, and when overexpressed, CDC25A can suppress activation of p38 and JNK1 and reduce cell death triggered specifically by oxidative stress (Zou et al, 2001). Whether other MAPKKK are also subject to such redox regulation is not clear, but a similar mechanism might function at the level of JNK to influence its activity.…”

Section: Sapk Pathwaysmentioning

confidence: 99%

Cellular response to oxidative stress: Signaling for suicide and survival*

Martindale

Holbrook

2002

Journal Cellular Physiology

2,091

1,596

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Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.

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The Cell Cycle-Regulatory CDC25A Phosphatase Inhibits Apoptosis Signal-Regulating Kinase 1

Cited by 91 publications

References 68 publications

Subcellular localisation of Cdc25A determines cell fate

Subcellular localisation of Cdc25A determines cell fate

Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1

Cellular response to oxidative stress: Signaling for suicide and survival*

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