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Mitotic arrest

Emily P Dawson, Denise G Lanza, Nicholas J Webster, Susan M Benton, Isao Suetake, Jason D Heaney
Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2 , a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice...
March 15, 2018: Development
Maeva Dufies, Damien Ambrosetti, Sonia Boulakirba, Anne Calleja, Coline Savy, Nathan Furstoss, Marwa Zerhouni, Julien Parola, Lazaro Aira-Diaz, Sandrine Marchetti, Francois Orange, Sandra Lacas-Gervais, Frederic Luciano, Arnaud Jacquel, Guillaume Robert, Gilles Pagès, Patrick Auberger
Polo-like kinases (Plks) define a highly conserved family of Ser/Thr kinases with crucial roles in the regulation of cell division. Here we show that Plk1 is cleaved by caspase 3, but not by other caspases in different hematopoietic cell lines treated with competitive inhibitors of the ATP-binding pocket of Plk1. Intriguingly, Plk1 was not cleaved in cells treated with Rigosertib, a non-competitive inhibitor of Plk1, suggesting that binding of the inhibitor to the ATP binding pocket of Plk1 triggers a conformational change and unmasks a cryptic caspase 3 cleavage site on the protein...
February 16, 2018: Oncotarget
Cher-Pheng Ooi, Terry K Smith, Eva Gluenz, Nadina Vasileva Wand, Sue Vaughan, Gloria Rudenko
The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post-mitotic cells dropped from (3...
March 13, 2018: Traffic
Jocelyn Charlton, Timothy L Downing, Zachary D Smith, Hongcang Gu, Kendell Clement, Ramona Pop, Veronika Akopian, Sven Klages, David P Santos, Alexander M Tsankov, Bernd Timmermann, Michael J Ziller, Evangelos Kiskinis, Andreas Gnirke, Alexander Meissner
Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission...
March 12, 2018: Nature Structural & Molecular Biology
Hanako Hayashi, Bungo Akiyoshi
Kinetoplastids have a nucleus that contains the nuclear genome and a kinetoplast that contains the mitochondrial genome. These single-copy organelles must be duplicated and segregated faithfully to daughter cells at each cell division. In Trypanosoma brucei , although duplication of both organelles starts around the same time, segregation of the kinetoplast precedes that of the nucleus. Cytokinesis subsequently takes place so that daughter cells inherit a single copy of each organelle. Very little is known about the molecular mechanism that governs the timing of these events...
March 12, 2018: Biology Open
Xiaoping Song, Xingxing Gao, Jiali Lu, Hongfang Liang, Peng Su, Qingwei Li, Yue Pang
High mobility group (HMG) box-containing protein 1 (HBP1) is a member of the HMG family of chromosomal proteins. Previous studies have shown that human HBP1 exhibits tumor-suppressor activity. Here, we identified a homologue of HBP1, L-hbp1, in Lampetra japonica. The L-hbp1 gene shared high sequence similarity with its homologues in jawed vertebrates, as shown by bioinformatics analyses. L-hbp1 contains a 1,584-bp open reading frame that encodes 527 amino acids. A pAdenox-L-HBP1 plasmid was constructed and transfected successfully in Raji cells, as revealed by real-time PCR...
March 8, 2018: Development, Growth & Differentiation
Zhi-Chuan Zhu, Ji-Wei Liu, Kui Li, Jing Zheng, Zhi-Qi Xiong
The nuclear import receptor karyopherin β1 (KPNB1) is involved in the nuclear import of most proteins and in the regulation of multiple mitotic events. Upregulation of KPNB1 has been observed in cancers including glioblastoma. Depletion of KPNB1 induces mitotic arrest and apoptosis in cancer cells, but the underlying mechanism is not clearly elucidated. Here, we found that downregulation and functional inhibition of KPNB1 in glioblastoma cells induced growth arrest and apoptosis without apparent mitotic arrest...
March 9, 2018: Oncogene
Anja Müller, Bernd Gillissen, Antje Richter, Anja Richter, Cindrilla Chumduri, Peter T Daniel, Christian W Scholz
Constitutive signaling of PI3K/Akt/mTOR plays a prominent role in malignant transformation and progression of B-cell non-Hodgkin lymphomas (B-NHL) underscoring the need for PI3K targeted therapies. The pan-class I PI3-kinase inhibitor BKM120 has shown preclinical activity in distinct malignancies and is currently tested in clinical trials. Intratumor heterogeneity is an intrinsic property of cancers that contributes to drug resistance and tumor recurrence. Here, we demonstrate that inhibition of PI3-kinases by BKM120 attenuates growth and survival of B-NHL cell lines by inducing mitotic arrest with subsequent induction of intrinsic apoptosis...
March 7, 2018: Cell Death & Disease
X-F Tang, X-L Zhou, Q Zhang, P Chen, C Lu, M-H Pan
Cyclin-dependent kinase inhibitors (CKIs) are negative regulators of the cell cycle. They can bind to cyclin-dependent kinase (CDK)-cyclin complexes and inhibit CDK activities. We identified a single homologous gene of the CDK interacting protein/kinase inhibitory protein (Cip/Kip) family, BmCKI, in the silkworm, Bombyx mori. The gene transcribes two splice variants: a 654-bp-long BmCKI-L (the longer splice variant) encoding a protein with 217 amino acids and a 579-bp-long BmCKI-S (the shorter splice variant) encoding a protein with 192 amino acids...
March 7, 2018: Insect Molecular Biology
Devi Amujuri, Bandi Siva, B Poornima, Katukuri Sirisha, A V S Sarma, V Lakshma Nayak, Ashok K Tiwari, U Purushotham, K Suresh Babu
A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38 μM which is comparable to the standard agent, doxorubicin...
February 24, 2018: European Journal of Medicinal Chemistry
Chen Qi, Xin Wang, Zhirong Shen, She Chen, Hong Yu, Noelle Williams, Gelin Wang
The commonly used antimitotic chemotherapeutic agents such as taxol and vinblastine arrest cell cycle progression by disrupting mitotic spindles, and cause cancer cells to undergo apoptosis through 'mitotic catastrophe'. The molecular mechanisms by which these drugs induce apoptosis and their relevance to clinical efficacy are not known. Facilitated by a new spindle poison diazonamide, we found that apoptosis induced by these agents requires death receptor 3 (DR3). Mitotic arrest by these agents induces lysosome-dependent secretion of the DR3 ligand, TL1A...
March 1, 2018: Cell Research
Ksenia Krupina, Charlotte Kleiss, Sushil Awal, Irene Rodriguez-Hernandez, Victoria Sanz-Moreno, Izabela Sumara
Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression...
2018: Molecular & Cellular Oncology
Kaushiki Chatterjee, Dina AlSharif, Christina Mazza, Palwasha Syar, Mohamed Al Sharif, Jimmie E Fata
Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed...
February 21, 2018: Nutrients
Raquel Azevedo, Eleazar Rodriguez, Rafael José Mendes, Nuno Mariz-Ponte, Sara Sario, José Carlos Lopes, José Miguel P Ferreira de Oliveira, Conceição Santos
Inorganic Mercury (Hg) contamination persists an environmental problem, but its cyto- and genotoxicity in plants remains yet unquantified. To determine the extent of Hg-induced cyto- and genotoxicity, and assess most sensitive endpoints in plants, Pisum sativum L. seedlings were exposed for 14 days to different HgCl2 concentrations up to 100 μM. Shoots and roots from hydroponic exposure presented growth impairment and/or morphological disorders for doses >1 μM, being the roots more sensitive. Plant growth, ploidy changes, clastogenicity (HPCV), cell cycle dynamics (G1 -S-G2 ), Comet-tail moment (TM), Comet-TD, Mitotic-index (MI) and cell proliferation index (CPI) were used to evaluate Hg-induced cyto/genotoxicity...
February 16, 2018: Plant Physiology and Biochemistry: PPB
Yuqing Shen, John William Sherman, Xuyong Chen, Ruoning Wang
From unicellular to multicellular organisms, cell cycle progression is tightly coupled to biosynthetic and bioenergetic demands. Accumulating evidence has demonstrated the G1/S phase transition as a key checkpoint where cells respond to their metabolic status and commit to replicating the genome. However, the mechanism underlying the coordination of metabolism and the G2/M phase transition in mammalian cells remains unclear. Here we show that the activation of AMP-activated protein kinase (AMPK), a highly conserved cellular energy sensor, significantly delays mitosis entry...
February 21, 2018: Journal of Biological Chemistry
Tara Byrne, Laura Nelson, James P Beirne, Daniel Sharpe, Jennifer E Quinn, W Glenn McCluggage, Tracy Robson, Fiona Furlong
OBJECTIVES: The aim of this study was to investigate the relationship between BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as determined by immunohistochemistry, and clinical outcomes in epithelial ovarian carcinoma (EOC). METHODS: A tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent...
March 2018: International Journal of Gynecological Cancer
Manuel Haschka, Gerlinde Karbon, Luca L Fava, Andreas Villunger
Interfering with mitosis for cancer treatment is an old concept that has proven highly successful in the clinics. Microtubule poisons are used to treat patients with different types of blood or solid cancer since more than 20 years, but how these drugs achieve clinical response is still unclear. Arresting cells in mitosis can promote their demise, at least in a petri dish. Yet, at the molecular level, this type of cell death is poorly defined and cancer cells often find ways to escape. The signaling pathways activated can lead to mitotic slippage, cell death, or senescence...
February 19, 2018: EMBO Reports
Zinnat Shahina, Amira M El-Ganiny, Jessica Minion, Malcolm Whiteway, Taranum Sultana, Tanya E S Dahms
Background: Cinnamon ( Cinnamomum zeylanicum) bark extract exhibits potent inhibitory activity against Candida albicans but the antifungal mechanisms of this essential oil remain largely unexplored. Results: We analyzed the impact of cinnamon bark oil on C. albicans RSY150, and clinical strains isolated from patients with candidemia and candidiasis. The viability of RSY150 was significantly compromised in a dose dependent manner when exposed to cinnamon bark oil, with extensive cell surface remodelling at sub inhibitory levels (62...
2018: Fungal Biology and Biotechnology
P Muthuraja, M Himesh, S Prakash, U Venkatasubramanian, P Manisankar
Kinesin Spindle Protein (KSP) or Eg5 is an essential kinesin that is involved in spindle separation process during mitosis and also unregulated in certain cancer cells. Inhibitors of this enzyme have proved to be effective to block spindle separation followed by mitotic arrest and apoptosis of the cancer cells. Since this enzyme has two allosteric inhibitor binding sites, it's an excellent target for developing drugs for cancer chemotherapy. Many pyrimidine derivatives have been proved to be active against cancer and other enzymes...
February 10, 2018: European Journal of Medicinal Chemistry
N Pokhrel, E Ben-Tal Cohen, O Genin, M Ruzal, D Sela-Donenfeld, Y Cinnamon
Storing eggs at low temperature prior to incubation is common practice in the broiler hatchery industry; however, prolonged storage (beyond 7 d) is known to increase early embryonic mortality and reduce chick quality and performance. To better understand the basis of this mortality, we previously published milestone criteria to evaluate morphological and cellular properties of the freshly laid embryo. Using these criteria, in the present study we checked the effects of storage at 18°C and 12°C for up to 28 d on hatchability and chick quality...
February 14, 2018: Poultry Science
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