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Cell Cycle

Vijay R Menon, Varsha Ananthapadmanabhan, Selene Swanson, Siddharth Saini, Fatmata Sesay, Vasily Yakovlev, Laurence Florens, James A DeCaprio, Michael P Washburn, Mikhail Dozmorov, Larisa Litovchick
Human Dual-specificity tyrosine (Y) Regulated Kinase 1A (DYRK1A) is encoded by a dosage dependent gene whereby either trisomy or haploinsufficiency result in developmental abnormalities. However, the function and regulation of this important protein kinase are not fully understood. Here, we report proteomic analysis of DYRK1A in human cells that revealed a novel role of DYRK1A in DNA double-strand breaks (DSBs) repair, mediated in part by its interaction with the ubiquitin-binding protein RNF169 that accumulates at the DSB sites and promotes homologous recombination repair (HRR) by displacing 53BP1, a key mediator of non-homologous end joining (NHEJ)...
February 17, 2019: Cell Cycle
Marta Płonka, Donata Wawrzycka, Robert Wysocki, Magdalena Boguta, Małgorzata Cieśla
Assembly of the RNA polymerases in both yeast and humans is proposed to occur in the cytoplasm prior to their nuclear import. Our previous studies identified a cold-sensitive mutation, rpc128-1007, in the yeast gene encoding the second largest Pol III subunit, Rpc128. rpc128-1007 is associated with defective assembly of Pol III complex and, in consequence, decreased level of tRNA synthesis. Here, we show that rpc128-1007 mutant cells remain largely unbudded and larger than wild type cells. Flow cytometry revealed that most rpc128-1007 mutant cells have G1 DNA content, suggesting that this mutation causes pronounced cell cycle delay in the G1 phase...
February 13, 2019: Cell Cycle
Carolyn K J Young, Matthew J Young
HepaRG is a proliferative human hepatoma-derived cell line that can be differentiated into hepatocyte-like and biliary-like cells. Differentiated HepaRG cultures maintain key hepatic functions including drug transporters and xenobiotic-metabolizing enzymes. To gain insight into proliferative and differentiated HepaRG metabolism we profiled various bioenergetic parameters and investigated cell culture levels of adenosine triphosphate (ATP), lactate, and lactate dehydrogenase (LDH) activity. Compared to differentiated-derived HepaRG, cells from proliferative cultures had increased basal and ATP-linked respiration and decreased maximal and spare respiratory capacities...
February 12, 2019: Cell Cycle
Man-Hei Cheung, Aftab Amin, Rentian Wu, Yan Qin, Lan Zou, Zhiling Yu, Chun Liang
Noc3p (Nucleolar Complex-associated protein) is an essential protein in budding yeast DNA replication licensing. Noc3p mediates the loading of Cdc6p and MCM proteins onto replication origins during the M-to-G1 transition by interacting with ORC (Origin Recognition Complex) and MCM (Minichromosome Maintenance) proteins. FAD24 (Factor for Adipocyte Differentiation, clone number 24), the human homolog of Noc3p (hNOC3), was previously reported to play roles in the regulation of DNA replication and proliferation in human cells...
February 11, 2019: Cell Cycle
Inma Quilis, Francisco J Taberner, Carlos A Martínez-Garay, Paula Alepuz, J Carlos Igual
The yeast β-karyopherin Msn5 controls the SBF cell-cycle transcription factor, responsible for the periodic expression of CLN2 cyclin gene at G1/S, and the nuclear export of Cln2 protein. Here we show that Msn5 regulates Cln2 by an additional mechanism. Inactivation of Msn5 causes a severe reduction in the cellular content of Cln2. This occurs by a post-transcriptional mechanism, since CLN2 mRNA level is not importantly affected in asynchronous cultures. Cln2 stability is not significantly altered in msn5 cells and inactivation of Msn5 causes a reduction in protein level even when Cln2 is stabilized...
February 11, 2019: Cell Cycle
Rosa Maisto, María Oltra, Lorena Vidal-Gil, Natalia Martínez-Gil, Javier Sancho-Pellúz, Clara Di Filippo, Settimio Rossi, Michele D Amico, Jorge Miguel Barcia, Francisco Javier Romero
ARPE-19 retinal pigment epithelial cells cultured in a medium containing 35 mM D-glucose led to an augmented ROS formation and release of vascular endothelial factor (VEGF)-containing exosomes compared to ARPE-19 cells cultured in a medium containing 5 mM D-glucose (standard medium). Exposing these cells to the melanocortin 5 receptor agonist (MCR5 ) PG-901 (10-10 M), for 9 d reduced ROS generation, the number of exosomes released and their VEGF content. In contrast, incubating the cells with the melanocortin receptor MCR1 agonist BMS-470539 (10-5  M) or with the mixed MCR3/4 agonist MTII (0...
February 9, 2019: Cell Cycle
Zi-Yun Yi, Qiu-Xia Liang, Tie-Gang Meng, Jian Li, Ming-Zhe Dong, Yi Hou, Ying-Chun Ouyang, Chun-Hui Zhang, Heide Schatten, Qing-Yuan Sun, Jie Qiao, Wei-Ping Qian
PKCβI, a member of the classical protein kinase C family, plays key roles in regulating cell cycle transition. Here, we report the expression, localization and functions of PKCβI in mouse oocyte meiotic maturation. PKCβI and p-PKCβI (phosphor-PKCβI) were expressed from germinal vesicle (GV) stage to metaphase II (MII) stage. Confocal microscopy revealed that PKCβI was localized in the GV and evenly distributed in the cytoplasm after GV breakdown (GVBD), and it was concentrated at the midbody at telophase in meiotic oocytes...
February 7, 2019: Cell Cycle
Chang Liu, YinYan Li, Minjie Wei, Lin Zhao, Yangyang Yu, Guang Li
Lung cancer is one of the most malignant cancers worldwide, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Thousands of biomarkers related to the survival and prognosis of patients with this cancer type have been investigated through database mining; however, the prediction effect of a single gene biomarker is not satisfactorily specific or sensitive. Thus, the present study aimed to develop a novel gene signature of prognostic values for patients with LUAD. Using a data-mining method, we performed expression profiling of 1145 mRNAs in large cohorts with LUAD (n=511) from The Cancer Genome Atlas database...
February 6, 2019: Cell Cycle
Evan R Zynda, Mitchell H Maloy, Eugene S Kandel
Kidney ischemia, characterized by insufficient supply of oxygen and nutrients to renal epithelial cells, is the main cause of acute kidney injury and an important contributor to mortality world-wide. Earlier research implicated a G-protein coupled receptor (NK1R) in the death of kidney epithelial cells in ischemia-like conditions. P21-associated kinase 1 (PAK1) is involved in signalling by several G-proteins. We explored the consequences of PAK1 inhibition for cell survival under the conditions of reduced glucose and oxygen...
February 6, 2019: Cell Cycle
Yue Du, Dan Yan, Yongliang Yuan, Jian Xu, Suhua Wang, Zhiheng Yang, Weiyan Cheng, Xin Tian, Quancheng Kan
Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with limited options for targeted therapy. The exploration of novel targeted therapies for combating ESCC is urgently needed. Cyclin-dependent kinases (CDKs) play important roles in the progression of cancers; however, the function of CDK11p110 (cyclin-dependent kinase 11p110 ) in ESCC is still unknown. Here, we investigated the effects and molecular mechanisms of CDK11p110 in the proliferation and growth of ESCC by examining the expression of CDK11p110 in ESCC tissues and by detecting phenotypic changes in ESCC cells after CDK11p110 knockdown or overexpression in vitro and in vivo...
February 5, 2019: Cell Cycle
Zhi-Hang Zhou, Qing-Liang Wang, Lin-Hong Mao, Xiao-Qin Li, Peng Liu, Jin-Wen Song, Xue Liu, Feng Xu, Jing Lei, Song He
The acidic extracellular microenvironment, namely acidosis, is a biochemical hallmark of solid tumors. However, the tumorigenicity, metastatic potential, gene expression profile and chromatin accessibility of acidosis-adapted colorectal cancer cells remain unknown. The colorectal cancer cell SW620 was cultured in acidic medium (pH 6.5) for more than 3 months to be acidosis-adapted (SW620-AA). In comparison to parental cells, SW620-AA cells exhibit enhanced tumorigenicity and liver metastatic potential in vivo...
February 4, 2019: Cell Cycle
Yue Liu, Songhua Xu, Xiuli Lian, Yang Su, Yuhuan Zhong, Ruimin Lv, Kaien Mo, Huimin Zhu, Xiaojiang Wang, Lixuan Xu, Shie Wang
Zygotic genome activation (ZGA) is one of the most critical events at the beginning of mammalian preimplantation embryo development (PED). The mechanisms underlying mouse ZGA remain unclear although it has been widely studied. In the present study, we identified that tricho-rhino-phalangeal syndrome 1 (TRPS1), an atypical GATA family member, is an important factor for ZGA in mouse PED. We found that the Trps1 mRNA level peaked at the one-cell stage while TRPS1 protein did so at the two/four-cell stage. Knockdown of Trps1 by the microinjection of Trps1 siRNA reduced the developmental rate of mouse preimplantation embryos by approximately 30%, and increased the expression of ZGA marker genes MuERV-L and Zscan4d via suppressing the expression of major histone markers H3K4me3 and H3K27me3...
February 2, 2019: Cell Cycle
Dong Hwan Ho, Wongi Seol, Ilhong Son
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (LB) in neurons. α-Synuclein (αSyn) is a major component of LB and promote the PD pathogenesis via its accumulation by the impaired proteasomal or autophagic clearance. Numerous studies have revealed that the reduction of proteasome activity and autophagy is accelerated by cellular senescence. Leucine-rich repeat kinase 2 (LRRK2) contributes to PD progression and its most prevalent mutation, G2019S LRRK2, increases its activity...
February 2, 2019: Cell Cycle
A J Durston
Hox temporal collinearity (TC) is a mysterious feature of embryogenesis. This article is opportune because of a recent challenge to TC's existence This challenge is examined and the evidence that TC does exist is presented. Its function is discussed. Temporal collinearity is thought to be important because it lays the basis for Hox spatial collinearity and the vertebrate A-P axial pattern. The time-space translation mechanism whereby this occurs is examined.
February 2, 2019: Cell Cycle
Xuan Zhang, Su-Jin Li, Ziyin Li, Cynthia Y He, Geoff Hide, De-Hua Lai, Zhao-Rong Lun
Trypanosoma (Herpetosoma) lewisi is a globally distributed rat trypanosome, currently considered as a zoonotic pathogen; however, a detailed understanding of the morphological events occurring during the cell cycle is lacking. This study aimed to investigate the cell cycle morphology and cleavage events of Trypanosoma lewisi (T. lewisi) during in vitro cultivation. By establishing in vitro cultivation of T. lewisi at 37°C, various cell morphologies and stages could be observed. We have provided a quantitative analysis of the morphological events during T...
February 2, 2019: Cell Cycle
Yang Zhang, Ling Wang, Lei Meng, Guangke Cao, Yu Wu
Sirtuin 6 (SIRT6) has the function of regulating autophagy. The aim of this study was to investigate the mechanism through which SIRT6 relieved acute kidney injury (AKI) caused by sepsis. The AKI model was established with lipopolysaccharides (LPS) using mice. Hematoxylin-eosin (HE) staining and streptavidin-perosidase (SP) staining was used to observe kidney tissue and test SIRT6 and LC3B proteins in kidney. Enzyme-linked immunosorbent assay (ELISA) was performed to detected the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations...
January 30, 2019: Cell Cycle
Chun-Yi Cho, Christina M Kelliher, Steven B Haase
Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a "pulse" of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APCCdh1 ...
January 22, 2019: Cell Cycle
Xiu-Hong Qin, Xiang Ma, Shi-Feng Fang, Zhen-Zhen Zhang, Jian-Min Lu
Fungal keratitis is a relatively common ocular disease requiring positive medical management combined with surgical intervention. Interleukin-17 (IL-17) was reported to promote the activation and mobilization of neutrophile granulocyte to foci of inflammation. This study investigated the effect of IL-17 production from Th17 cells on the progression of fungal keratitis. A mouse model of fungal keratitis induced by Candida albicans was successfully constructed to detect infiltration of inflammatory cells in corneal tissues by hematoxylin-eosin (HE) staining and immunohistochemistry...
January 20, 2019: Cell Cycle
Shuman Huang, Dong Dong, Yaqian Zhang, Zhuo Chen, Jing Geng, Yulin Zhao
The aim of this study was to investigate the role of lncRNA NEAT1 (nuclear enriched abundant transcript 1) in regulating Th2 cell differentiation. The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. The mRNA expressions of ITCH and STAT6 were analyzed by qRT-PCR and western blotting. The levels of Th2 cytokines were detected by ELISA assay. RIP and ChIP assays were performed to analyze the association between NEAT1 and EZH2 as well as EZH2 and STAT6, respectively...
January 17, 2019: Cell Cycle
Jaewoo Choi, Nan Zhou, Luca Busino
The ubiquitin proteasome system (UPS) plays a critical function in cellular homeostasis. The misregulation of UPS is often found in human diseases, including cancer. Kelch-like protein 6 (KLHL6) is an E3 ligase gene mutated in diffused large B-cell lymphoma (DLBCL). This review discusses the function of KLHL6 as a cullin3-RING ligase and how cancer-associated mutations disrupt the interaction with the cullin3, resulting in the loss of KLHL6 function. Furthermore, the mRNA decay factor Roquin2 is discussed as the first bona fide substrate of KLHL6 in the context of B-cell receptor activation and B-cell lymphoma...
January 15, 2019: Cell Cycle
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