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https://www.readbyqxmd.com/read/29044420/characterization-of-a-novel-role-for-the-dynamin-mechanoenzymes-in-the-regulation-of-human-sperm-acrosomal-exocytosis
#1
Wei Zhou, Amanda L Anderson, Adrian P Turner, Geoffry N De Iuliis, Adam McCluskey, Eileen A McLaughlin, Brett Nixon
STUDY QUESTION: Does dynamin regulate human sperm acrosomal exocytosis? SUMMARY ANSWER: Our studies of dynamin localization and function have implicated this family of mechanoenzymes in the regulation of progesterone-induced acrosomal exocytosis in human spermatozoa. WHAT IS KNOWN ALREADY: Completion of an acrosome reaction is a prerequisite for successful fertilization in all studied mammalian species. It follows that failure to complete this unique exocytotic event represents a common aetiology in the defective spermatozoa of male infertility patients that have failed IVF in a clinical setting...
October 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29044141/cdk2-strengthens-the-intra-s-checkpoint-and-counteracts-cell-cycle-exit-induced-by-dna-damage
#2
Katarina Bačević, Gérald Lossaint, Thiziri Nait Achour, Virginie Georget, Daniel Fisher, Vjekoslav Dulić
Although cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and promotes DNA replication, it is dispensable for cell cycle progression due to redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be revealed in certain genetic backgrounds and it was reported to promote the G2/M DNA damage response checkpoint in TP53 (p53)-deficient cancer cells. However, in p53-proficient cells subjected to DNA damage, Cdk2 is inactivated by the CDK inhibitor p21. We therefore investigated whether Cdk2 differentially affects checkpoint responses in p53-proficient and deficient cell lines...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026105/mcph1-mutated-in-primary-microcephaly-is-required-for-efficient-chromosome-alignment-during-mitosis
#3
M Arroyo, R Kuriyama, M Trimborn, D Keifenheim, A Cañuelo, A Sánchez, D J Clarke, J A Marchal
MCPH1 gene, mutated in primary microcephaly, regulates cell progression into mitosis. While this role has been extensively investigated in the context of DNA damage, its function during unperturbed cell cycles has been given less attention. Here we have analyzed the dynamics of chromosome condensation and cell cycle progression in MCPH1 deficient cells under undamaging conditions. Our study demonstrates that chromosome condensation is uncoupled from cell cycle progression when MCPH1 function is lacking, resulting in cells that prematurely condense their chromosomes during mid G2-phase and delay decondensation at the completion of mitosis...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#4
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025019/differing-molecular-response-of-young-and-advanced-maternal-age-human-oocytes-to-ivm
#5
J M Reyes, E Silva, J L Chitwood, W B Schoolcraft, R L Krisher, P J Ross
STUDY QUESTION: What effect does maternal age have on the human oocyte's molecular response to in vitro oocyte maturation? SUMMARY ANSWER: Although polyadenylated transcript abundance is similar between young and advanced maternal age (AMA) germinal vesicle (GV) oocytes, metaphase II (MII) oocytes exhibit a divergent transcriptome resulting from a differential response to in vitro oocyte maturation. WHAT IS KNOWN ALREADY: Microarray studies considering maternal age or maturation stage have shown that either of these factors will affect oocyte polyadenylated transcript abundance in human oocytes...
September 15, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29021609/a-cdk1-gradient-guides-surface-contraction-waves-in-oocytes
#6
Johanna Bischof, Christoph A Brand, Kálmán Somogyi, Imre Májer, Sarah Thome, Masashi Mori, Ulrich S Schwarz, Péter Lénárt
Surface contraction waves (SCWs) in oocytes and embryos lead to large-scale shape changes coupled to cell cycle transitions and are spatially coordinated with the cell axis. Here, we show that SCWs in the starfish oocyte are generated by a traveling band of myosin II-driven cortical contractility. At the front of the band, contractility is activated by removal of cdk1 inhibition of the RhoA/RhoA kinase/myosin II signaling module, while at the rear, contractility is switched off by negative feedback originating downstream of RhoA kinase...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28982797/calibrated-mitotic-oscillator-drives-motile-ciliogenesis
#7
Adel Al Jord, Asm Shihavuddin, Raphaël Servignat d'Aout, Marion Faucourt, Auguste Genovesio, Anthi Karaiskou, Joëlle Sobczak-Thépot, Nathalie Spassky, Alice Meunier
Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the Cdk1-APC/C axis, spatiotemporally coordinates this reorganization in dividing cells. Here, we discovered that non-dividing cells could also implement this mitotic clock-like regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse brain multiciliated cells. These post-mitotic progenitors fine-tuned mitotic oscillator activity to drive the orderly progression of centriole production, maturation and motile ciliation while avoiding the mitosis commitment threshold...
October 5, 2017: Science
https://www.readbyqxmd.com/read/28982702/phosphatase-regulated-recruitment-of-the-spindle-and-kinetochore-associated-ska-complex-to-kinetochores
#8
Sushama Sivakumar, Gary J Gorbsky
Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The Spindle and Kinetochore-Associated (Ska) Complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases, Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores...
October 5, 2017: Biology Open
https://www.readbyqxmd.com/read/28980703/interleukin-1-receptor-associated-kinase-1-correlates-with-metastasis-and-invasion-in-endometrial-carcinoma
#9
Yilin Wang, Yanyan Wang, Xianzhi Duan, Yinuo Wang, Zhenyu Zhang
Endometrial carcinoma (EC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of interleukin-1 receptor-associated kinase 1 (IRAK1) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of IRAK1 in EC. In this study, IRAK1 was found elevated in EC compared with normal tissues. Further, high IRAK1 expression level was correlated with higher tumor stage, lymph node metastasis, myometrial invasion and lower survival rate...
October 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28979815/whole-exome-wide-association-study-identifies-a-missense-variant-in-slc2a4rg-associated-with-glioblastoma-risk
#10
Yingjie Zhao, Dapeng Yun, Xiang Zou, Tao Jiang, Gang Li, Lingna Hu, Juxiang Chen, Jianfeng Xu, Ying Mao, Hongyan Chen, Daru Lu
In this study, we conducted a genome-wide scan of single nucleotide polymorphisms (SNPs) to identify coding variants that is associated with the risk of glioblastoma (GBM), the most common and most malignant subtype of glioma. We genotyped 1038 GBM cases and 1008 controls in a Chinese Han population using Illumina HumanExome Beadchip v1.0. A missense variant, rs8957 (E[GAG]233D[GAU], SLC2A4RG, 20q13.33), was found being associated with GBM risk, with an odd ratio (OR) of 1.43 (95% confidence interval (CI) = 1...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28977921/docking-of-cdk1-with-antibiotic-drugs-revealed-novel-therapeutic-value-in-breast-ductal-cancer-in-situ
#11
Zhong-Hai Ding, Jia Qi, An-Quan Shang, Yu-Jie Zhang, Jun Wei, Li-Qing Hu, Wei-Wei Wang, Man Yang
The aim of our research is to identify potential genes associated with Ductal carcinoma in situ (DCIS) through microarrays. The microarray dataset GS54665 were downloaded from the GEO(Gene Expression Omnibus) database. Dysregulated genes were screened and their associations with DCIS was analyzed by comprehensive bioinformatics tools. A total of 649 differential expression genes were identified between normal and DCIS samples, including 224 up-regulated genes and 425 down-regulated genes. Biological process annotation and pathway enrichment analysis identified several DCIS-related signaling pathways...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969025/identification-of-genes-and-pathways-in-nasopharyngeal-carcinoma-by-bioinformatics-analysis
#12
Fang Chen, Congxiang Shen, Xiaoqi Wang, Huigang Wang, Yanhui Liu, Chaosheng Yu, Jieyu Lv, Jingjing He, Zhong Wen
Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966725/praja-is-overexpressed-in-glioblastoma-and-contributes-to-neural-precursor-development
#13
Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Bhargava Chitti, Amee A Kapadia, Neha Rana, Lopa Mishra, Chu-Xia Deng, Shuyun Rao, Bibhuti Mishra
PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3...
July 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28958992/identification-of-mek162-as-a-radiosensitizer-for-the-treatment-of-glioblastoma
#14
Ravi S Narayan, Ana Gasol, Paul L G Slangen, Fleur M G Cornelissen, Tonny Lagerweij, Hou Y Y E Veldman, Rogier Dik, Jaap van den Berg, Ben J Slotman, Thomas Wurdinger, Daphne Haas-Kogan, Lukas J A Stalpers, Brigitta G Baumert, Bart Westerman, Jan Theys, Peter Sminia
Glioblastoma (GBM) is a highly aggressive and lethal brain cancer type. PI3K and MAPK inhibitors have been studied pre-clinically in GBM as monotherapy, but not in combination with radiotherapy, which is a key component of the current standard treatment of GBM. In our study, GBM cell lines and patient representative primary cultures were grown as multicellular spheroids. Spheroids were treated with a panel of small molecule drugs including MK2206, RAD001, BEZ235, MLN0128 and MEK162, alone and in combination with irradiation...
September 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28950208/exploration-of-cell-cycle-regulation-and-modulation-of-the-dna-methylation-mechanism-of-pelargonidin-insights-from-the-molecular-modeling-approach
#15
Natesan Karthi, Arumugasamy Karthiga, Thangaraj Kalaiyarasu, Antony Stalin, Vaiyapuri Manju, Sanjeev Kumar Singh, Ravi Cyril, Sang-Myeong Lee
Pelargonidin is an anthocyanidin isolated from plant resources. It shows strong cytotoxicity toward various cancer cell lines, even though the carcinogenesis-modulating pathway of pelargonidin is not yet known. One of our previous reports showed that pelargonidin arrests the cell cycle and induces apoptosis in HT29 cells. Flowcytometry and immunoblot analysis confirmed that pelargonidin specifically inhibits the activation of CDK1 and blocks the G2-M transition of the cell cycle. In addition, DNA fragmentation was observed along with induction of cytochrome c release-mediated apoptosis...
August 8, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28949903/protein-kinases-responsible-for-the-phosphorylation-of-the-nuclear-egress-core-complex-of-human-cytomegalovirus
#16
Eric Sonntag, Jens Milbradt, Adriana Svrlanska, Hanife Strojan, Sigrun Häge, Alexandra Kraut, Anne-Marie Hesse, Bushra Amin, Uwe Sonnewald, Yohann Couté, Manfred Marschall
Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear egress complex (NEC) assembled by a heterodimer of two essential viral core egress proteins. In the case of human cytomegalovirus (HCMV), this core NEC is defined by the interaction between the membrane-anchored pUL50 and its nuclear cofactor, pUL53. NEC protein phosphorylation is considered to be an important regulatory step, so this study focused on the respective role of viral and cellular protein kinases. Multiply phosphorylated pUL50 varieties were detected by Western blot and Phos-tag analyses as resulting from both viral and cellular kinase activities...
September 27, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28946554/mir-181a-inhibits-non-small-cell-lung-cancer-cell-proliferation-by-targeting-cdk1
#17
Qin Shi, Zhan Zhou, Naishu Ye, Qiaolin Chen, Xiuxia Zheng, Minshan Fang
BACKGROUND: MicroRNAs (miRNAs) emerge as important regulators involved in malignant progression in some tumors. MiR-181a has been found to function as a tumor suppressor in some tumors including non-small cell lung cancer (NSCLC). However, the functional role of miR-181a in NSCLC still needed to be investigated. METHODS: The expression of miR-181a were determined by qRT-PCR, the association between miR-181a and clinicopathological data were performed by chi-square test and survival analysis were evaluated by Kaplan-Meier curve and log rank test...
September 8, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28944822/investigation-of-crucial-genes-and-micrornas-in-conventional-osteosarcoma-using-gene-expression-profiling-analysis
#18
Chuangang Peng, Qi Yang, Bo Wei, Baoming Yuan, Yong Liu, Yuxiang Li, Dawer Gu, Guochao Yin, Bo Wang, Dehui Xu, Xuebing Zhang, Daliang Kong
The present study aimed to screen potential genes associated with conventional osteosarcoma (OS) and obtain further information on the pathogenesis of this disease. The microarray dataset GSE14359 was downloaded from the Gene Expression Omnibus. A total of 10 conventional OS samples and two non‑neoplastic primary osteoblast samples in the dataset were selected to identify the differentially expressed genes (DEGs) using the Linear Models for Microarray Data package. The potential functions of the DEGs were predicted using Gene Ontology (GO) and pathway enrichment analyses...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28935119/effects-of-cdk-inhibitors-on-the-maturation-transcription-and-mpf-activity-of-porcine-oocytes
#19
Reza K Oqani, Tao Lin, Jae Eun Lee, So Yeon Kim, Jung Won Kang, Dong Il Jin
In mammals, cyclin-dependent kinases (CDKs) are involved in regulating both the cell cycle and transcription. Although CDK1 is known to act as the kinase subunit of maturation-promoting factor (MPF), the roles of the other CDKs in mammalian oocyte maturation are not yet understood. Here, we show that inhibition of various CDKs by small molecule inhibitors has different effects on the maturation and transcriptional activity of pig oocytes in vitro. Inhibition of CDK1 did not significantly affect cumulus cell expansion, but its kinase activity was necessary for germinal vesicle breakdown (GVBD)...
September 18, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/28931595/cell-cycle-transitions-a-common-role-for-stoichiometric-inhibitors
#20
Michael Hopkins, John J Tyson, Béla Novák
The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called 'checkpoints'), if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors...
September 20, 2017: Molecular Biology of the Cell
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