scholarly journals Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1

2003 ◽  
Vol 374 (2) ◽  
pp. 349-358 ◽  
Author(s):  
Yuan ZHOU ◽  
Yick-Pang CHING ◽  
Raymond W. M. NG ◽  
Dong-Yan JIN
Keyword(s):  
Cell Cycle ◽  
Differential Expression ◽  
Cultured Cells ◽  
Cyclin A ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Cycle Arrest ◽  
Localization Signal ◽  
Alternatively Spliced

The timely destruction of key regulators through ubiquitin-mediated proteolysis ensures the orderly progression of the cell cycle. The APC (anaphase-promoting complex) is a major component of this degradation machinery and its activation is required for the execution of critical events. Recent studies have just begun to reveal the complex control of the APC through a regulatory network involving WD40 repeat proteins CDC20 and CDH1. In the present paper, we report on the identification and characterization of human CDH1β, a novel alternatively spliced isoform of CDH1. Both CDH1α and CDH1β can bind to the APC and stimulate the degradation of cyclin B1, but they are differentially expressed in human tissues and cells. CDH1α contains a nuclear localization signal which is absent in CDH1β. Intracellularly, CDH1α appears in the nucleus whereas CDH1β is a predominantly cytoplasmic protein. The forced overexpression of CDH1α in cultured cells correlates with the reduction of nuclear cyclin A, but the steady-state amount of cyclin A does not change noticeably in CDH1β-overexpressed cells. In Xenopus embryos, ectopic overexpression of human CDH1α, but not of CDH1β, induces cell-cycle arrest during the first G1 phase at the mid-blastula transition. Taken together, our findings document the differential expression, subcellular localization and cell-cycle-regulatory activity of human CDH1 isoforms.

scholarly journals Glypican-1 Regulates Anaphase Promoting Complex/Cyclosome Substrates and Cell Cycle Progression in Endothelial Cells

2008 ◽  
Vol 19 (7) ◽  
pp. 2789-2801 ◽  
Author(s):  
Dianhua Qiao ◽  
Xinhai Yang ◽  
Kristy Meyer ◽  
Andreas Friedl
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
Biochemical Analyses

Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 causes cell cycle arrest at mitosis or the G2 phase of the cell cycle, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase-promoting complex/cyclosome (APC/C)–mediated degradation of mitotic cyclins and securin. High levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations that are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C-mediated degradation of mitotic cyclins and securin.

Differential expression of protein phosphatase type 1 isotypes and nucleolin during cell cycle arrest

2007 ◽  
Vol 25 (4) ◽  
pp. 369-375 ◽  
Author(s):  
Hiroyuki Morimoto ◽  
Akiko Ozaki ◽  
Hirohiko Okamura ◽  
Kaya Yoshida ◽  
Bruna Rabelo Amorim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Differential Expression ◽  
Protein Phosphatase ◽  
Cycle Arrest ◽  
Protein Phosphatase Type 1 ◽  
Protein Phosphatase Type

scholarly journals Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Jian-Hong Lin ◽  
Pei-Ching Ting ◽  
Wen-Sen Lee ◽  
Hung-Wen Chiu ◽  
Chun-An Chien ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
P53 Protein ◽  
Acid Methyl Ester ◽  
Cyclin B1 ◽  
Cycle Arrest ◽  
Acid Methyl ◽  
M Phase ◽  
Intracellular Ca ◽  
Palmitic Acid Methyl Ester

Bone marrow-derived mesenchymal cells (BM-MSCs) are able to differentiate into adipocytes, which can secrete adipokines to affect BM-MSC proliferation and differentiation. Recent evidences indicated that adipocytes can secrete fatty acid metabolites, such as palmitic acid methyl ester (PAME), which is able to cause vasorelaxation and exerts anti-inflammatory effects. However, effects of PAME on BM-MSC proliferation remain unclear. The aim of this study was to investigate the effect of PAME on human BM-MSC (hBM-MSC) proliferation and its underlying molecular mechanisms. hBM-MSCs were treated with PAME for 48 h and then subjected to various analyses. The results from the present study show that PAME significantly reduced the levels of G2/M phase regulatory proteins, cyclin-dependent kinase 1 (Cdk1), and cyclin B1 and inhibited proliferation in hBM-MSCs. Moreover, the level of Mdm2 protein decreased, while the levels of p21 and p53 protein increased in the PAME-treated hBM-MSCs. However, PAME treatment did not significantly affect apoptosis/necrosis, ROS generation, and the level of Cdc25C protein. PAME also induced intracellular acidosis and increased intracellular Ca2+ levels. Cotreatment with PAME and Na+/H+ exchanger inhibitors together further reduced the intracellular pH but did not affect the PAME-induced decreases of cell proliferation and increases of the cell population at the G2/M phase. Cotreatment with PAME and a calcium chelator together inhibited the PAME-increased intracellular Ca2+ levels but did not affect the PAME-induced cell proliferation inhibition and G2/M cell cycle arrest. Moreover, the half-life of p53 protein was prolonged in the PAME-treated hBM-MSCs. Taken together, these results suggest that PAME induced p53 stabilization, which in turn increased the levels of p53/p21 proteins and decreased the levels of Cdk1/cyclin B1 proteins, thereby preventing the activation of Cdk1, and eventually caused cell cycle arrest at the G2/M phase. The findings from the present study might help get insight into the physiological roles of PAME in regulating hBM-MSC proliferation.

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.

scholarly journals Characterization of the Akt2 Domain Essential for Binding Nuclear p21cip1 to Promote Cell Cycle Arrest during Myogenic Differentiation

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76987 ◽  
Author(s):  
Lisa Heron-Milhavet ◽  
Celine Franckhauser ◽  
Anne Fernandez ◽  
Ned J. Lamb
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Myogenic Differentiation ◽  
Cycle Arrest

scholarly journals Cell-cycle arrest in Jurkat leukaemic cells: a possible role for docosahexaenoic acid

2003 ◽  
Vol 371 (2) ◽  
pp. 621-629 ◽  
Author(s):  
Rafat A. SIDDIQUI ◽  
Laura J. JENSKI ◽  
Kevin A. HARVEY ◽  
Jacqueline D. WIESEHAN ◽  
William STILLWELL ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Docosahexaenoic Acid ◽  
Cell Cycle Arrest ◽  
Protein Phosphatase ◽  
Cyclin A ◽  
Low Doses ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Cdk2 Activity ◽  
Leukaemic Cells

Docosahexaenoic acid (DHA) is known to have anti-cancer activities by mechanisms that are not well understood. In the present study, we test one possible pathway for DHA action in Jurkat leukaemic cells. Low doses of DHA (10μM) are shown to induce cell-cycle arrest, whereas higher doses are cytotoxic. However, when cells that were pre-treated with 10μM DHA are given an additional 10μM DHA dose, cell viability rapidly decreases. Immunoblotting reveals that repeated low doses of DHA results in activation of caspase 3, implying induction of apoptosis. DHA (10μM) is shown to increase ceramide levels after 6h of incubation and, after 24h, the cells appear to be arrested in S phase. With DHA, the amount of phosphorylated retinoblastoma protein (pRb) decreases significantly. Western blot analysis also shows that DHA greatly reduces the level of cyclin A, while increasing the level of p21 WAF1, a cellular inhibitor of cyclin A/cyclin-dependent kinase 2 (cdk2) activity. Furthermore, the observed DHA-induced doubling of the ratio of hypophosphorylated pRb (hypo-pRb) to total pRb is inhibited by tautomycin and phosphatidic acid (PA), known inhibitors of protein phosphatase 1 (PP1), and by the PP2 inhibitor okadaic acid. The present study demonstrates one possible connected pathway for DHA action. By this pathway, low doses of DHA increase ceramide levels, which leads to inhibition of cdk2 activity and stimulation of PP1 and PP2A. The net effect of cdk2 inhibition and protein phosphatase activation is an inhibition of pRb phosphorylation, consequently arresting Jurkat cell growth.

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.

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