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https://www.readbyqxmd.com/read/28072388/a-sequential-multi-target-mps1-phosphorylation-cascade-promotes-spindle-checkpoint-signaling
#1
Zhejian Ji, Haishan Gao, Luying Jia, Bing Li, Hongtao Yu
The master spindle checkpoint kinase Mps1 directly senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C(Cdc20)) to delay anaphase onset...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28045167/cdc20sirna-and-paclitaxel-co-loaded-nanometric-liposomes-of-a-nipecotic-acid-derived-cationic-amphiphile-inhibit-xenografted-neuroblastoma
#2
Sukanya Bhunia, Vegesna Radha, Arabinda Chaudhuri
Despite significant recent progress in the area of translational genomics of neuroblastoma, the overall survival rates for children with high-risk NB continue to be not more than 5 years due to tumor relapse and/or drug-resistant tumors. Herein we report on the development of a neuroblastoma targeting nanometric (130-150 nm) circulation stable liposomal system prepared from a novel nipecotic acid-derived cationic amphiphile (NACA). The size ranges of liposomes (130-150 nm) were confirmed by both dynamic light scattering and transmission electron microscopy...
January 3, 2017: Nanoscale
https://www.readbyqxmd.com/read/28017606/generation-of-a-spindle-checkpoint-arrest-from-synthetic-signaling-assemblies
#3
Ivan Yuan, Ioanna Leontiou, Priya Amin, Karen M May, Sadhbh Soper Ní Chafraidh, Eliška Zlámalová, Kevin G Hardwick
The spindle checkpoint acts as a mitotic surveillance system, monitoring interactions between kinetochores and spindle microtubules and ensuring high-fidelity chromosome segregation [1-3]. The checkpoint is activated by unattached kinetochores, and Mps1 kinase phosphorylates KNL1 on conserved MELT motifs to generate a binding site for the Bub3-Bub1 complex [4-7]. This leads to dynamic kinetochore recruitment of Mad proteins [8, 9], a conformational change in Mad2 [10-12], and formation of the mitotic checkpoint complex (MCC: Cdc20-Mad3-Mad2 [13-15])...
January 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28007967/aberrant-meiotic-modulation-partially-contributes-to-the-lower-germination-rate-of-pollen-grains-in-maize-zea-mays-l-under-low-nitrogen-supply
#4
Hongyan Zheng, Huamao Wu, Xiaoying Pan, Weiwei Jin, Xuexian Li
Pollen germination is an essential step towards successful pollination during maize reproduction. How low niutrogen (N) affects pollen germination remains an interesting biological question to be addressed. We found that only low N resulted in a significantly lower germination rate of pollen grains after 4 weeks of low N, phosphorus or potassium treatment in maize production. Importantly, cytological analysis showed 7-fold more micronuclei in male meiocytes under the low N treatment than in the control, indicating that the lower germination rate of pollen grains was partially due to numerous chromosome loss events resulting from preceding meiosis...
November 15, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28004426/inhibition-of-anaphase-promoting-complex-by-silence-apc-ccdh1to-enhance-radiosensitivity-of-nasopharyngeal-carcinoma-cells
#5
Chunmiao Wang, Zhengying Su, Huaxin Hou, Danrong Li, Zhiyu Pan, Wei Tian, Chunyan Mo
The aim of this study was to investigate the possibility of APC/C(Cdh1) as a potential therapeutic target in the radiosensitivity of nasopharyngeal carcinoma(NPC) cell CNE-1, and explain the role of APC subunits after silence of Cdh1 combined with radiotherapy. Transfection with Cdh1 shRNA significantly increased the radiosensitivity of CNE-1 cells and the radiation enhancement ratio (RER) of sh-Cdh1 cells was 1.76. Knockdown of Cdh1 in CNE-1 cells increased irradiation induced apoptosis and G2/M phase cell cycle arrest...
December 22, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28003474/phylogenomics-guided-discovery-of-a-novel-conserved-cassette-of-short-linear-motifs-in-bubr1-essential-for-the-spindle-checkpoint
#6
Eelco Tromer, Debora Bade, Berend Snel, Geert J P L Kops
The spindle assembly checkpoint (SAC) maintains genomic integrity by preventing progression of mitotic cell division until all chromosomes are stably attached to spindle microtubules. The SAC critically relies on the paralogues Bub1 and BubR1/Mad3, which integrate kinetochore-spindle attachment status with generation of the anaphase inhibitory complex MCC. We previously reported on the widespread occurrences of independent gene duplications of an ancestral 'MadBub' gene in eukaryotic evolution and the striking parallel subfunctionalization that lead to loss of kinase function in BubR1/Mad3-like paralogues...
December 2016: Open Biology
https://www.readbyqxmd.com/read/27991546/apc-c-cdc20-and-apc-c-play-pivotal-roles-in-the-process-of-embryonic-development-in-artemia-sinica
#7
Mengchen Zhang, Feng Yao, Hong Luan, Wei Zhao, Ting Jing, Shuang Zhang, Lin Hou, Xiangyang Zou
Anaphase Promoting Complex or Cyclosome (APC/C) is a representative E3 ubiquitin ligase, triggering the transition of metaphase to anaphase by regulating degradation and ensures the exit from mitosis. Cell division cycle 20 (CDC20) and Cell division cycle 20 related protein 1 (CDH1), as co-activators of APC/C, play significant roles in the spindle assembly checkpoint, guiding ubiquitin-mediated degradation, together with CDC23. During the embryonic development of the brine shrimp, Artemia sinica, CDC20, CDH1 and CDC23 participate in cell cycle regulation, but the specific mechanisms of their activities remain unknown...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939943/the-mitotic-checkpoint-complex-requires-an-evolutionary-conserved-cassette-to-bind-and-inhibit-active-apc-c
#8
Barbara Di Fiore, Claudia Wurzenberger, Norman E Davey, Jonathon Pines
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27780719/prostate-cancer-associated-mutation-in-spop-impairs-its-ability-to-target-cdc20-for-poly-ubiquitination-and-degradation
#9
Fei Wu, Xiangpeng Dai, Wenjian Gan, Lixin Wan, Min Li, Nicholas Mitsiades, Wenyi Wei, Qiang Ding, Jinfang Zhang
Recent studies revealed that mutations in SPOP (Speckle-type POZ protein) occur in up to 15% of patients with prostate cancer. However, the physiological role of SPOP in regulating prostate tumorigenesis remains elusive. Here, we identified the Cdc20 oncoprotein as a novel ubiquitin substrate of SPOP. As such, pharmacological inhibition of Cullin-based E3 ligases by MLN4924 could stabilize endogenous Cdc20 in cells. Furthermore, we found that Cullin 3, and, to a less extent, Cullin 1, specifically interacted with Cdc20...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27742609/a-novel-mutation-in-the-n-terminal-domain-of-drosophila-bubr1-affects-the-spindle-assembly-checkpoint-function-of-bubr1
#10
Marie Duranteau, Jean-Jacques Montagne, Zohra Rahmani
The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate segregation of chromosomes into two daughter cells. BubR1, a key component of the SAC, also plays a role in the mitotic timing since depletion of BubR1 leads to accelerated mitosis. We previously found that mutation of the KEN1-box domain of Drosophila BubR1 (bubR1-KEN1 mutant) affects the binding of BubR1 to Cdc20, the activating co-factor of the APC/C, and does not accelerate the mitotic timing despite resulting in a defective SAC, which was unlike what was reported in mammalian cells...
November 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27741356/miip-haploinsufficiency-induces-chromosomal-instability-and-promotes-tumour-progression-in-colorectal-cancer
#11
Yan Sun, Ping Ji, Tao Chen, Xinhui Zhou, Da Yang, Yuhong Guo, Yuexin Liu, Limei Hu, Dianren Xia, Yanxue Liu, Asha S Multani, Ilya Shmulevich, Raju Kucherlapati, Scott Kopetz, Anil K Sood, Stanley R Hamilton, Baocun Sun, Wei Zhang
The gene encoding migration and invasion inhibitory protein (MIIP), located on 1p36.22, is a potential tumour suppressor gene in glioma. In this study, we aimed to explore the role and mechanism of action of MIIP in colorectal cancer (CRC). MIIP protein expression gradually decreased along the colorectal adenoma-carcinoma sequence and was negatively correlated with lymph node and distant metastasis in 526 colorectal tissue samples (p < 0.05 for all). Analysis of The Cancer Genome Atlas (TCGA) data showed that decreased MIIP expression was significantly associated with MIIP hemizygous deletion (p = 0...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27694041/investigating-ego-modules-involved-in-tgf%C3%AE-3-induced-chondrogenesis-in-mesenchymal-stem-cells-based-on-ego-network
#12
Jing-Guo Wu, Qing-Wei Jia, Yong Li, Fei-Fei Cao, Xi-Shan Zhang, Cong Liu
OBJECTIVE: This paper aimed to investigate ego modules for TGFβ3-induced chondrogenesis in mesenchymal stem cells (MSCs) using ego network algorithm. METHODS: The ego network algorithm comprised three parts, extracting differential expression network (DEN) based on gene expression data and protein-protein interaction (PPI) data; exploring ego genes by reweighting DEN; and searching ego modules by ego gene expansions. Subsequently, permutation test was carried out to evaluate the statistical significance of the ego modules...
September 28, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27664031/c-terminal-region-of-mad2-plays-an-important-role-during-mitotic-spindle-checkpoint-in-fission-yeast-schizosaccharomyces-pombe
#13
Gaurav Kumar Singh, Sharanbasappa Shrimant Karade, Rajeev Ranjan, Nafees Ahamad, Shakil Ahmed
The mitotic arrest deficiency 2 (Mad2) protein is an essential component of the spindle assembly checkpoint that interacts with Cdc20/Slp1 and inhibit its ability to activate anaphase promoting complex/cyclosome (APC/C). In bladder cancer cell line the C-terminal residue of the mad2 gene has been found to be deleted. In this study we tried to understand the role of the C-terminal region of mad2 on the spindle checkpoint function. To envisage the role of C-terminal region of Mad2, we truncated 25 residues of Mad2 C-terminal region in fission yeast S...
September 23, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27633058/silencing-of-cdc20-suppresses-metastatic-castration-resistant-prostate-cancer-growth-and-enhances-chemosensitivity-to-docetaxel
#14
Ke Li, Yunhua Mao, Li Lu, Cheng Hu, Dejuan Wang, Jie Si-Tu, Minhua Lu, Shubin Peng, Jianguang Qiu, Xin Gao
The role of cell division cycle 20 (CDC20) was investigated in chemoresistance to decetaxel and the underlying mechanisms in metastatic castration-resistant prostate cancer (mCRPC). MTT assays were performed to determine effects of siRNA-mediated CDC20 knockdown on cell proliferation and anticancer activity of docetaxel. Western blot analyses were conducted to detect changes of Akt and Wnt signaling. Furthermore, in vivo growth of PCa was examined in nude mice treated with siCDC20 or docetaxel alone or in combination...
October 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27626499/rottlerin-inhibits-cell-growth-and-invasion-via-down-regulation-of-cdc20-in-glioma-cells
#15
Lixia Wang, Yingying Hou, Xuyuan Yin, Jingna Su, Zhe Zhao, Xiantao Ye, Xiuxia Zhou, Li Zhou, Zhiwei Wang
Rottlerin, isolated from a medicinal plant Mallotus phillippinensis, has been demonstrated to inhibit cellular growth and induce cytoxicity in glioblastoma cell lines through inhibition of calmodulin-dependent protein kinase III. Emerging evidence suggests that rottlerin exerts its antitumor activity as a protein kinase C inhibitor. Although further studies revealed that rottlerin regulated multiple signaling pathways to suppress tumor cell growth, the exact molecular insight on rottlerin-mediated tumor inhibition is not fully elucidated...
September 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27623074/infrank-a-ranking-based-identification-of-influential-genes-in-biological-networks
#16
Xiuliang Cui, Xiaofeng Li, Jin Li, Xue Wang, Wen Sun, Zhuo Cheng, Jin Ding, Hongyang Wang
Capturing the predominant driver genes is critical in the analysis of high-throughput experimental data; however, existing methods scarcely include the unique characters of biological networks. Herein we introduced a ranking-based computational framework (inFRank) to rank the proteins by their influence. Using inFRank, we identified the top 20 influential genes in hepatocellular carcinoma (HCC). Network analysis revealed a prominent community composed of 7 influential genes. Intriguingly, five genes among the community were critical for mitotic spindle assembly checkpoint (SAC), suggesting that dysregulation of SAC could be a distinct feature of HCC and targeting SAC-associated genes might be a promising therapeutic strategy...
September 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27618268/bub3-bub1-binding-to-spc7-knl1-toggles-the-spindle-checkpoint-switch-by-licensing-the-interaction-of-bub1-with-mad1-mad2
#17
Maria Del Mar Mora-Santos, America Hervas-Aguilar, Katharina Sewart, Theresa C Lancaster, John C Meadows, Jonathan B A Millar
The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C)...
October 10, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27614924/effect-of-liquid-helium-vitrification-on-the-ultrastructure-and-related-gene-expression-of-mature-bovine-oocytes-after-vitrifying-at-immature-stage
#18
Hua Wu, Xue-Li Yu, Xian-Fei Guo, Fan Zhang, Xu-Zhe Pei, Xiao-Xia Li, Wen-Xia Han, Ying-Hua Li
This study aimed to investigate the developmental potential of and the ultrastructural changes and gene expression differences resulting from liquid helium (LHe; -269 °C) vitrification in immature bovine oocytes. Immature oocytes were randomly divided into three groups: fresh oocytes (control, negative control), oocytes vitrified in liquid nitrogen (LN group, positive control), and oocytes vitrified in LHe (LHe group). In experiment 1, the rates of normal morphology, maturation, cleavage, and blastocyst in the LHe group were higher than those in the LN group (87...
January 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/27610375/integrated-analysis-of-dna-methylation-and-mrna-expression-profiles-data-to-identify-key-genes-in-lung-adenocarcinoma
#19
Xiang Jin, Xingang Liu, Xiaodan Li, Yinghui Guan
Introduction. Lung adenocarcinoma (LAC) is the most frequent type of lung cancer and has a high metastatic rate at an early stage. This study is aimed at identifying LAC-associated genes. Materials and Methods. GSE62950 downloaded from Gene Expression Omnibus included a DNA methylation dataset and an mRNA expression profiles dataset, both of which included 28 LAC tissue samples and 28 adjacent normal tissue samples. The differentially expressed genes (DEGs) were screened by Limma package in R, and their functions were predicted by enrichment analysis using TargetMine online tool...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27601587/dhx33-transcriptionally-controls-genes-involved-in-the-cell-cycle
#20
Baolei Yuan, Xingshun Wang, Chunyan Fan, Jin You, Yuchu Liu, Jason D Weber, Hanbing Zhong, Yandong Zhang
The RNA helicase DHX33 has been shown to be a critical regulator of cell proliferation and growth. However, the underlying mechanisms behind DHX33 function remain incompletely understood. We present original evidence in multiple cell lines that DHX33 transcriptionally controls the expression of genes involved in the cell cycle, notably cyclin, E2F1, cell division cycle (CDC), and minichromosome maintenance (MCM) genes. DHX33 physically associates with the promoters of these genes and controls the loading of active RNA polymerase II onto these promoters...
December 1, 2016: Molecular and Cellular Biology
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