14-3-3 Proteins Act as Negative Regulators of the Mitotic Inducer Cdc25 in<i>Xenopus</i>Egg Extracts

Kumagai, Akiko; Yakowec, P.; Dunphy, William G.

doi:10.1091/mbc.9.2.345

Cited by 204 publications

(226 citation statements)

References 49 publications

(66 reference statements)

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“…Studies of the interaction between Cdc25B and 14-3-3 clearly demonstrated that the binding of 14-3-3 masks the NLS of Cdc25B, thereby causing nuclear exclusion of the protein without affecting its phosphatase activity. Similar results were obtained with Xenopus Cdc25 (Kumagai et al, 1998;Kumagai and Dunphy, 1999;Yang et al, 1999). In Xenopus oocytes, PKA phosphorylated Cdc25-S287, resulting in direct interaction between Cdc25 with 14-3-3 and sequestration of Cdc25 away from its substrate, MPF, which would leave MPF inactive.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

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

Zhang

et al. 2008

Developmental Dynamics

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“…Cdc25C S287A cannot be phosphorylated by Chk1 and induces checkpoint-arrested egg extracts to enter mitosis (Kumagai et al, 1998b). The S287A mutant efficiently suppresses the cell cycle arrest caused by geminin depletion in a dose-dependent manner, as determined by the size and appearance of the embryonic cells after the MBT ( Figure 5B, top, black rectangles).…”

Section: Bypassing Chk1 Pathway Suppresses G2 Arrest Caused By Geminimentioning

confidence: 98%

“…Injection of the highest concentration of wild-type Cdc25C RNA partially suppresses the cell cycle arrest ( Figure 5B, top, gray rectangles) and partially reverses the phosphorylation of Cdc2 on tyrosine-15 (bottom, lane 7). Because phosphorylation of S287 does not inhibit phosphatase activity (Kumagai et al, 1998b), wild-type Cdc25C would be able to overcome the arrest once sufficient quantities were available to saturate the amount of 14-3-3 in the cytoplasm. Immunoblots showed that comparable amounts of the Cdc25C WT and S287A proteins were expressed at each RNA concentration (our unpublished data).…”

Section: Bypassing Chk1 Pathway Suppresses G2 Arrest Caused By Geminimentioning

confidence: 99%

Geminin Deficiency Causes a Chk1-dependent G2 Arrest inXenopus

McGarry

2002

MBoC

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Geminin is an unstable inhibitor of DNA replication that gets destroyed at the metaphase/ anaphase transition. The biological function of geminin has been difficult to determine because it is not homologous to a characterized protein and has pleiotropic effects when overexpressed. Geminin is thought to prevent a second round of initiation during S or G2 phase. In some assays, geminin induces uncommitted embryonic cells to differentiate as neurons. In this study, geminin was eliminated from developing Xenopus embryos by using antisense techniques. Geminindeficient embryos show a novel and unusual phenotype: they complete the early cleavage divisions normally but arrest in G2 phase immediately after the midblastula transition. The arrest requires Chk1, the effector kinase of the DNA replication/DNA damage checkpoint pathway. The results indicate that geminin has an essential function and that loss of this function prevents entry into mitosis by a Chk1-dependent mechanism. Geminin may be required to maintain the structural integrity of the genome or it may directly down-regulate Chk1 activity. The data also show that during the embryonic cell cycles, rereplication is almost entirely prevented by gemininindependent mechanisms.

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“…The 14-3-3 proteins bind to phosphorylated Ser-216 of Cdc25C and induce Cdc25C export from the nucleus during interphase in response to DNA damage, 7,8 but they have no apparent effect on Cdc25C phosphatase activity. 9,10 In addition, hyperphosphorylation of Cdc25C correlates to its enhanced phosphatase activity. 11 Most studies with Cdc25C have focused on its role in mitotic progression.…”

mentioning

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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14-3-3 Proteins Act as Negative Regulators of the Mitotic Inducer Cdc25 inXenopusEgg Extracts

Cited by 204 publications

References 49 publications

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

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

Geminin Deficiency Causes a Chk1-dependent G2 Arrest inXenopus

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

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