A novel role for glycogen synthase kinase-3 in Xenopus development: maintenance of oocyte cell cycle arrest by a beta-catenin-independent mechanism

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 567-576 ◽  
Author(s):  
D.L. Fisher ◽  
N. Morin ◽  
M. Doree
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Glycogen Synthase ◽  
Cyclin B1 ◽  
Dominant Negative ◽  
Glycogen Synthase Kinase ◽  
Beta Catenin ◽  
Xenopus Development ◽  
Cycle Arrest ◽  
Cell Cycle Inhibition

We have examined the expression of glycogen synthase kinase-3beta in oocytes and early embryos of Xenopus and found that the protein is developmentally regulated. In resting oocytes, GSK-3beta is active and it is inactivated on maturation in response to progesterone. GSK-3beta inactivation is necessary and rate limiting for the cell cycle response to this hormone and the subsequent accumulation of beta-catenin. Overexpression of a dominant negative form of the kinase accelerates maturation, as does inactivation by expression of Xenopus Dishevelled or microinjection of an inactivating antibody. Cell cycle inhibition by GSK-3beta is not mediated by the level of beta-catenin or by a direct effect on either the MAP kinase pathway or translation of mos and cyclin B1. These data indicate a novel role for GSK-3beta in Xenopus development: in addition to controlling specification of the dorsoventral axis in embryos, it mediates cell cycle arrest in oocytes.

scholarly journals Type III Secretion-Dependent Cell Cycle Block Caused in HeLa Cells by Enteropathogenic Escherichia coliO103

2001 ◽  
Vol 69 (11) ◽  
pp. 6785-6795 ◽  
Author(s):  
Jean-Philippe Nougayrède ◽  
Michèle Boury ◽  
Christian Tasca ◽  
Olivier Marchès ◽  
Alain Milon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Hela Cells ◽  
Dna Content ◽  
Significant Proportion ◽  
Focal Adhesions ◽  
Cyclin B1 ◽  
Stress Fibers ◽  
Cycle Arrest ◽  
Cell Cycle Inhibition

ABSTRACT Rabbit enteropathogenic Escherichia coli (EPEC) O103 induces in HeLa cells an irreversible cytopathic effect characterized by the recruitment of focal adhesions, formation of stress fibers, and inhibition of cell proliferation. We have characterized the modalities of the proliferation arrest and investigated its underlying mechanisms. We found that HeLa cells that were exposed to the rabbit EPEC O103 strain E22 progressively accumulated at 4C DNA content and did not enter mitosis. A significant proportion of the cells were able to reinitiate DNA synthesis without division, leading to 8C DNA content. This cell cycle inhibition by E22 was abrogated in mutants lacking EspA, -B, and -D and was restored by transcomplementation. In contrast, intimin and Tir mutants retained the antiproliferative effect. The cell cycle arrest was not a direct consequence of the formation of stress fibers, since their disruption by toxins during exposure to E22 did not reverse the cell cycle inhibition. Likewise, the cell cycle arrest was not dependent on the early tyrosine dephosphorylation events triggered by E22 in the cells. Two key partner effectors controlling entry into mitosis were also investigated: cyclin B1 and the associated cyclin-dependent kinase 1 (Cdk1). Whereas cyclin B1 was not detectably affected in E22-exposed cells, Cdk1 was maintained in a tyrosine-phosphorylated inactive state and lost its affinity for p13 suc1 -agarose beads. This shows that Cdk1 is implicated in the G2/M arrest caused by EPEC strain E22.

scholarly journals The Antiangiogenic Factor, 16-kDa Human Prolactin, Induces Endothelial Cell Cycle Arrest by Acting at Both the G0–G1 and the G2–M Phases

2005 ◽  
Vol 19 (7) ◽  
pp. 1932-1942 ◽  
Author(s):  
Sébastien P. Tabruyn ◽  
Ngoc-Quynh-Nhu Nguyen ◽  
Anne M. Cornet ◽  
Joseph A. Martial ◽  
Ingrid Struman
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Glycogen Synthase ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Cyclin B1 ◽  
Cycle Arrest ◽  
Human Prolactin

Abstract The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a potent antiangiogenic factor that has been shown to prevent tumor growth in a xenograph mouse model. In this paper we first demonstrate that 16K hPRL inhibits serum-induced DNA synthesis in adult bovine aortic endothelial cells. This inhibition is associated with cell cycle arrest at both the G0–G1 and the G2–M phase. Western blot analysis revealed that 16K hPRL strongly decreases levels of cyclin D1 and cyclin B1, but not cyclin E. The effect on cyclin D1 is at least partially transcriptional, because treatment with 16K hPRL both reduces the cyclin D1 mRNA level and down-regulates cyclin D1 promoter activity. This regulation may be due to inhibition of the MAPK pathway, but it is independent of the glycogen synthase kinase-3β pathway. Lastly, 16K hPRL induces the expression of negative cell cycle regulators, the cyclin-dependent kinase inhibitors p21(cip1) and p27(kip1). In summary, 16K hPRL inhibits serum-induced proliferation of endothelial cells through combined effects on positive and negative regulators of cell cycle progression.

scholarly journals The Novel Nature Microtubule Inhibitor Ivalin Induces G2/M Arrest and Apoptosis in Human Hepatocellular Carcinoma SMMC-7721 Cells In Vitro

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 470 ◽  
Author(s):  
Fangyuan Liu ◽  
Shiqi Lin ◽  
Caiyun Zhang ◽  
Jiahui Ma ◽  
Zhuo Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Western Blotting ◽  
Network Formation ◽  
Cyclin B1 ◽  
Human Hepatocellular Carcinoma ◽  
Microtubule Depolymerization ◽  
Microtubule Network ◽  
Cycle Arrest

Background and Objectives: Microtubules are an attractive target for cancer chemotherapy. Previously, we reported that Ivalin exhibited excellent anti-migration and anti-invasion activities in human breast cancer cells. Here, we examined the microtubule inhibition effect of Ivalin in human hepatocellular carcinoma SMMC-7721 cells. Materials and Methods: We used the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the cell proliferation effect of Ivalin and flow cytometry analysis to detect the apoptotic and cell cycle arrest effects of Ivalin. Immunofluorescence staining was used to measure the effect of Ivalin on the cytoskeleton network, and Western blotting was used to detect the expression levels of Bax, Bcl-2, Cdc2, phosphor-Cdc2, Cdc25A, Cyclin B1, and tubulin. Results: Ivalin induced cell cycle G2/M arrest and subsequent triggered apoptosis in human hepatocellular carcinoma SMMC-7721 cells. Furthermore, microtubules were shown to be involved in Ivalin-meditated apoptosis. In this connection, Ivalin treatment suppressed cellular microtubule network formation by regulating microtubule depolymerization. Moreover, Western blotting revealed Cdc25A and Cyclin B1 were upregulated in Ivalin-meditated cell cycle arrest. Subsequently, the induction of Bax (a proapoptotic protein) and reduction of Bcl-2 (an anti-apoptotic protein) expression were observed in Ivalin-treated SMMC-7721 cells. Conclusion: Ivalin induced microtubule depolymerization, then blocked cells in mitotic phase, and eventually resulted in apoptosis in SMMC-7721 cells. Collectively, these data indicate that Ivalin, acting as a novel inhibitor of microtubules, could be considered as a promising lead in anticancer drug development.

SMBA1, a Bax Activator, Induces Cell Cycle Arrest and Apoptosis in Malignant Glioma Cells

Pharmacology ◽  
2019 ◽  
Vol 105 (3-4) ◽  
pp. 164-172
Author(s):  
Shuangbo Fan ◽  
Qian Xu ◽  
Liang Wang ◽  
Yulin Wan ◽  
Sheng Qiu
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Biological Effects ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Apoptosis Pathway ◽  
Cycle Arrest ◽  
Intrinsic Apoptosis Pathway ◽  
Induced Apoptosis ◽  
Dose Dependent

SMBA1 (small-molecule Bax agonists 1), a small molecular activator of Bax, is a potential anti-tumour agent. In the present study, we investigated the biological effects of SMBA1 on glioblastoma (GBM) cells. SMBA1 reduced the viabilities of U87MG, U251 and T98G cells in a time- and dose-dependent manner. Moreover, treatment with SMBA1 induced cell cycle arrest at the G2/M phase transition, accompanied by the downregulation of Cdc25c and cyclin B1 and the upregulation of p21. SMBA1 also induced apoptosis of GBM cells in a dose-dependent manner. Mechanistically, SMBA1 induced apoptosis via the intrinsic pathway. Silencing of Bax or ectopic expression of Bcl-2 significantly inhibited SMBA1-induced apoptosis. Moreover, SMBA1 inhibited the growth of U87MG xenograft tumours in vivo. Overall, SMBA1 shows anti-proliferative effects against GBM cells through activation of the intrinsic apoptosis pathway.

scholarly journals Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression.

1996 ◽  
Vol 183 (4) ◽  
pp. 1663-1668 ◽  
Author(s):  
S Mohapatra ◽  
X Yang ◽  
J A Wright ◽  
E A Turley ◽  
A H Greenberg
Keyword(s):  
Cell Cycle ◽  
Lung Metastases ◽  
Growth Control ◽  
Cyclin B1 ◽  
Mrna Degradation ◽  
Dominant Negative ◽  
Protein Levels ◽  
Cycle Arrest ◽  
Important Regulator ◽  
Extracellular Matrix Receptors

The hyaluronan (HA) receptor RHAMM is an important regulator of cell growth. Overexpression of RHAMM is transforming and is required for H-ras transformation. The molecular mechanism underlying growth control by RHAMM and other extracellular matrix receptors remains largely unknown. We report that soluble RHAMM induces G2/M arrest by suppressing the expression of Cdc2/Cyclin B1, a protein kinase complex essential for mitosis. Down-regulation of RHAMM by use of dominant negative mutants or antisense of mRNA also decreases Cdc2 protein levels. Suppression of Cdc2 occurs as a result of an increased rate of cdc2 mRNA degradation. Moreover, tumor cells treated with soluble RHAMM are unable to form lung metastases. Thus, we show that mitosis is directly linked to RHAMM through control of Cdc2 and Cyclin B1 expression. Failure to sustain levels of Cdc2 and Cyclin B1 proteins leads to cell cycle arrest.

scholarly journals Glycogen Synthase Kinase-3 and Omi/HtrA2 Induce Annexin A2 Cleavage followed by Cell Cycle Inhibition and Apoptosis

2009 ◽  
Vol 20 (19) ◽  
pp. 4153-4161 ◽  
Author(s):  
Chi-Yun Wang ◽  
Yee-Shin Lin ◽  
Wu-Chou Su ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin
Keyword(s):  
Cell Cycle ◽  
Serine Proteases ◽  
Glycogen Synthase ◽  
Annexin A2 ◽  
Glycogen Synthase Kinase ◽  
Serum Withdrawal ◽  
Cellular Processes ◽  
Cell Cycle Inhibition ◽  
Necrotic Region ◽  
Induced Apoptosis

Annexin A2 is involved in multiple cellular processes, including cell survival, growth, division, and differentiation. A lack of annexin A2 makes cells more sensitive to apoptotic stimuli. Here, we demonstrate a potential mechanism for apoptotic stimuli-induced annexin A2 cleavage, which contributes to cell cycle inhibition and apoptosis. Annexin A2 was persistently expressed around the proliferative but not the necrotic region in BALB/c nude mice with human lung epithelial carcinoma cell A549-derived tumors. Knockdown expression of annexin A2 made cells susceptible to either serum withdrawal-induced cell cycle inhibition or cisplatin-induced apoptosis. Under apoptotic stimuli, annexin A2 was time-dependently cleaved. Mechanistic studies have shown that protein phosphatase 2A (PP2A)-activated glycogen synthase kinase (GSK)-3 is essential for this process. Therefore, inhibiting GSK-3 reversed serum withdrawal-induced cell cycle inhibition and cisplatin-induced apoptosis. Furthermore, inhibiting serine proteases blocked apoptotic stimuli-induced annexin A2 cleavage. Bax activation and Mcl-1 destabilization, which is regulated by PP2A and GSK-3, caused annexin A2 cleavage via an Omi/HtrA2-dependent pathway. Taking these results together, we conclude that GSK-3 and Omi/HtrA2 synergistically cause annexin A2 cleavage and then cell cycle inhibition or apoptosis.

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