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https://www.readbyqxmd.com/read/28925395/small-molecules-targeted-to-the-microtubule-hec1-interaction-inhibit-cancer-cell-growth-through-microtubule-stabilization
#1
M Ferrara, G Sessa, M Fiore, F Bernard, I A Asteriti, E Cundari, G Colotti, S Ferla, M Desideri, S Buglioni, D Trisciuoglio, D Del Bufalo, A Brancale, F Degrassi
Highly expressed in cancer protein 1 (Hec1) is a subunit of the kinetochore (KT)-associated Ndc80 complex, which ensures proper segregation of sister chromatids at mitosis by mediating the interaction between KTs and microtubules (MTs). HEC1 mRNA and protein are highly expressed in many malignancies as part of a signature of chromosome instability. These properties render Hec1 a promising molecular target for developing therapeutic drugs that exert their anticancer activities by producing massive chromosome aneuploidy...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28916740/mad2b-acts-as-a-negative-regulatory-partner-of-tcf4-on-proliferation-in-human-dermal-papilla-cells
#2
Nanlan Yu, Zhiqiang Song, Kezhou Zhang, Xichuan Yang
Dermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915666/ard1-mediated-aurora-kinase-a-acetylation-promotes-cell-proliferation-and-migration
#3
Tam Thuy Lu Vo, Ji-Hyeon Park, Ji Hae Seo, Eun Ji Lee, Hoon Choi, Sung-Jin Bae, Hoang Le, Sunho An, Hye Shin Lee, Hee-Jun Wee, Kyu-Won Kim
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915607/coal-tar-pitch-extract-could-induce-chromosomal-instability-of-human-bronchial-epithelial-cells-mediated-by-spindle-checkpoint-related-proteins
#4
Peng Zhang, Zhitao Li, Na Wang, Guangcai Duan, Wei Wang, Yanming Feng, Yong Zhao, Lixia Wang, Hansong Zhu, Qiao Zhang, Xiaozhuan Liu, Weidong Wu, Yongjun Wu, Wu Yao, Jing Wang, Yiming Wu, Feifei Feng
Coal tar pitch (CTP) is a byproduct of coal tar distillation. The workers working with coal tar or in aluminum smelters, potrooms and carbon plants have the opportunities of exposing to coal tar pitch volatiles. Coal tar pitches from which polycyclic aromatic hydrocarbons (PAHs) originate have been shown to exhibit lung carcinogenicity in humans. Chromosomal instability (CIN) is a mechanism in carcinogenesis, however, whether CIN is involved in coal tar pitch-induced lung cancer remains elusive. In this present study, human bronchial epithelial cells (BEAS-2B) were first exposed to coal tar pitch extracts (CTPE) to induce a malignant transformation model...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913178/modeling-cancer-cell-growth-dynamics-in-vitro-in-response-to-antimitotic-drug-treatment
#5
Alexander Lorz, Dana-Adriana Botesteanu, Doron Levy
Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28904335/brca2-suppresses-replication-stress-induced-mitotic-and-g1-abnormalities-through-homologous-recombination
#6
Weiran Feng, Maria Jasin
Mutations in the tumor suppressor BRCA2 predominantly predispose to breast cancer. Paradoxically, while loss of BRCA2 promotes tumor formation, it also causes cell lethality, although how lethality is triggered is unclear. Here, we generate BRCA2 conditional non-transformed human mammary epithelial cell lines using CRISPR-Cas9. Cells are inviable upon BRCA2 loss, which leads to replication stress associated with under replication, causing mitotic abnormalities, 53BP1 nuclear body formation in the ensuing G1 phase, and G1 arrest...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28901377/anthocyanin%C3%A2-rich-blackcurrant-extract-inhibits-proliferation-of-the-mcf10a-healthy-human-breast-epithelial-cell-line-through-induction-of-g0-g1-arrest-and-apoptosis
#7
Naoki Nanashima, Kayo Horie, Mitsuru Chiba, Manabu Nakano, Hayato Maeda, Toshiya Nakamura
Blackcurrants (Ribes nigrum L., Grossulariaceae) possess a high content of anthocyanin polyphenols, which have been demonstrated to exhibit beneficial effects on health due to their antioxidant and anticarcinogenic prope-rties. The present study investigated novel functions of anthocyanin‑rich blackcurrant extracts (BCEs) in a healthy mammary epithelial cell line, MCF10A. The percentages of viable cells were 85, 75, 53 and 31% following exposure to 50, 100, 200 and 400 µg/ml BCE, respectively. The half‑maximal response concentration of BCE was 237...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899455/mitotic-arrest-deficient-protein-2b-overexpressed-in-lung-cancer-promotes-proliferation-emt-and-metastasis
#8
Hua Zhang, Xiuquan He, Wenfei Yu, Bingqing Yue, Ziting Yu, Ying Qin
As the non-catalytic subunit of mammalian DNA polymerase, mitotic arrest-deficient protein 2B (MAD2B) has been reportedto play a role in cell-cycle regulation, DNA damage tolerance, gene expression and carcinogenesis. Although its expression is known to be associated with poor prognosis in several types of human cancers, the significance of MAD2B expression in lung malignancies is still unclear. Our study showed that MAD2B expression significantly increased in lung cancer, especially in the metastatic tissues...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28887307/dynamic-feature-of-mitotic-arrest-deficient-2-like-protein-2-mad2l2-and-structural-basis-for-its-interaction-with-chromosome-alignment-maintaining-phosphoprotein-camp
#9
Kodai Hara, Shota Taharazako, Masanori Ikeda, Hiroki Fujita, Yoshiko Mikami, Sotaro Kikuchi, Asami Hishiki, Hideshi Yokoyama, Yoshinobu Ishikawa, Shin-Ichiro Kanno, Kozo Tanaka, Hiroshi Hashimoto
Mitotic arrest deficient 2-like protein 2 (MAD2L2), also termed MAD2B or REV7, is involved in multiple cellular functions including translesion DNA synthesis (TLS), signal transduction, transcription, and mitotic events. MAD2L2 interacts with chromosome alignment-maintaining phosphoprotein (CAMP), a kinetochore-microtubule attachment protein in mitotic cells, presumably through a novel "WK" motif in CAMP. Structures of MAD2L2 in complex with binding regions of the TLS proteins REV3 and REV1 have revealed that MAD2L2 has two faces for protein-protein interactions (PPIs) that are regulated by its C-terminal region; however, the mechanisms underlying the MAD2L2-CAMP interaction and the mitotic role of MAD2L2 remain unknown...
September 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28884079/podophyllotoxin-a-novel-potential-natural-anticancer-agent
#10
REVIEW
Hamidreza Ardalani, Amir Avan, Majid Ghayour-Mobarhan
OBJECTIVE: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX) as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. MATERIALS AND METHODS: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016...
July 2017: Avicenna Journal of Phytomedicine
https://www.readbyqxmd.com/read/28881742/eribulin-alone-or-in-combination-with-the-plk1-inhibitor-bi-6727-triggers-intrinsic-apoptosis-in-ewing-sarcoma-cell-lines
#11
Lilly Magdalena WeiΔ, Manuela Hugle, Simone Fulda
In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878066/cytological-analysis-of-cytoplasmic-incompatibility-induced-by-cardinium-suggests-convergent-evolution-with-its-distant-cousin-wolbachia
#12
Marco Gebiola, Massimo Giorgini, Suzanne E Kelly, Matthew R Doremus, Patrick M Ferree, Martha S Hunter
Cytoplasmic incompatibility (CI) is a conditional sterility in numerous arthropods that is caused by inherited, intracellular bacteria such as Wolbachia Matings between males carrying CI-inducing Wolbachia and uninfected females, or between males and females infected with different Wolbachia strains, result in progeny that die during very early embryogenesis. Multiple studies in diploid (Drosophila) and haplodiploid (Nasonia) insects have shown that CI-Wolbachia cause a failure of the paternally derived chromatin from resolving into distinct chromosomes...
September 13, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28851440/plk1-is-essential-for-proper-chromosome-segregation-during-meiosis-i-meiosis-ii-transition-in-pig-oocytes
#13
Zixiao Zhang, Changchao Chen, Liying Ma, Qiuchen Yu, Shuai Li, Benazir Abbasi, Jiayi Yang, Rong Rui, Shiqiang Ju
BACKGROUND: Polo-like kinase 1 (Plk1), as a characteristic regulator in meiosis, organizes multiple biological events of cell division. Although Plk1 has been implicated in various functions in somatic cell mitotic processes, considerably less is known regarding its function during the transition from metaphase I (MI) to metaphase II (MII) stage in oocyte meiotic progression. METHODS: In this study, the possible role of Plk1 during the MI-to-MII stage transition in pig oocytes was addressed...
August 29, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28843738/exposure-of-spermatozoa-to-dibutyl-phthalate-induces-abnormal-embryonic-development-in-a-marine-invertebrate-galeolaria-caespitosa-polychaeta-serpulidae
#14
Yonggang Lu, Minjie Lin, Robert John Aitken
In this study, we have investigated the impact of dibutyl phthalate (DBP) on early embryogenesis in a sessile marine invertebrate, Galeolaria caespitosa. DBP was found to induce sperm dysfunction as well as impaired and defective embryogenesis characterised by a particular pattern of abnormality. Thus, after the first cleavage, one blastomere in these abnormal embryos was able to carry out further mitoses, while the other arrested. Analysis of microtubules, chromosomes and actin filaments demonstrated that the mitotic spindles in the abnormal embryos were irregularly bent, shortened and unable to anchor to the cortex, resulting in the defective segregation of chromosomes...
August 19, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28842672/downregulation-of-parp1-transcription-by-promoter-associated-e2f4-rbl2-hdac1-brm-complex-contributes-to-repression-of-pluripotency-stem-cell-factors-in-human-monocytes
#15
Wiśnik Ewelina, Płoszaj Tomasz, Robaszkiewicz Agnieszka
Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assembly of an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex which deacetylates nucleosomes and compacts chromatin. In G1 arrested cells, PARP1 transcription is reduced by the recruitment of E2F1-RB1-HDAC1-EZH2(PRC2)-BRM/BRG1(SWI/SNF), which additionally trimethylates H3K27 and causes an even higher increase in nucleosome density...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842252/e3-ubiquitin-ligase-dtx4-is-required-for-adipogenic-differentiation-in-3t3-l1-preadipocytes-cell-line
#16
Zonggui Wang, Zhong Dai, Yaqiong Pan, Simin Wu, Zhengli Li, Changqing Zuo
Deltex4 (DTX4) is a member of the Deltex family of proteins. To date several lines of evidences suggest that Deltex family of proteins is closely linked to cell development and cell differentiation. However, little is known about the role of DTX4 in adipogenic differentiation. In this study, we assessed the impact of DTX4 on adipogenic differentiation in vitro, we found that DTX4 protein expression gradually increased during adipogenic differentiation of 3T3-L1 preadipocytes cell line. While DTX4 stable knockdown by recombinant shRNA lentivirus (sh-DTX4) notably reduced the number of lipid droplets and down-regulated the expression of adipogenic transcription factors C/EBPα and PPARγ and adipogenic markers gene FABP4 and Adipsin...
August 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28833071/emerging-mechanisms-regulating-mitotic-synchrony-during-animal-embryogenesis
#17
REVIEW
Yosuke Ogura, Yasunori Sasakura
The basic mechanisms controlling mitosis are highly conserved in animals regardless of cell types and developmental stages. However, an exceptional aspect of mitosis is seen during early animal embryogenesis in which a large fertilized egg is quickly divided into smaller blastomeres according to the reproducible spatiotemporal pattern that does not rely on the cell-cycle arrest or growth. This mitosis, referred to as cleavage, overlaps in the timeframe with the specification of cell fate. The precise spatiotemporal regulation of cleavages is therefore essential to the creation of the appropriate cell number and to the morphology of an embryo...
September 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28819014/cyclin-a2-modulates-kinetochore-microtubule-attachment-in-meiosis-ii
#18
Qing-Hua Zhang, Wai Shan Yuen, Deepak Adhikari, Jennifer A Flegg, Greg FitzHarris, Marco Conti, Piotr Sicinski, Ibtissem Nabti, Petros Marangos, John Carroll
Cyclin A2 is a crucial mitotic Cdk regulatory partner that coordinates entry into mitosis and is then destroyed in prometaphase within minutes of nuclear envelope breakdown. The role of cyclin A2 in female meiosis and its dynamics during the transition from meiosis I (MI) to meiosis II (MII) remain unclear. We found that cyclin A2 decreases in prometaphase I but recovers after the first meiotic division and persists, uniquely for metaphase, in MII-arrested oocytes. Conditional deletion of cyclin A2 from mouse oocytes has no discernible effect on MI but leads to disrupted MII spindles and increased merotelic attachments...
August 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28818995/maternal-dcaf2-is-crucial-for-maintenance-of-genome-stability-during-the-first-cell-cycle-in-mice
#19
Yi-Wen Xu, Lan-Rui Cao, Min Wang, Ying Xu, Xin Wu, Junping Liu, Chao Tong, Heng-Yu Fan
Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin 4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by LoxP sequences, and specifically deleted Dcaf2 in oocytes...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28815566/maturation-promoting-factor-destabilization-mediates-human-chorionic-gonadotropin-induced-meiotic-resumption-in-rat-oocytes
#20
Meenakshi Tiwari, Shail K Chaube
Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs)...
September 2017: Development, Growth & Differentiation
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