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https://www.readbyqxmd.com/read/29903833/functional-analysis-of-short-linear-motifs-in-the-plant-cyclin-dependent-kinase-inhibitor-siamese
#1
Narender Kumar, Renee Dale, Daniel Kemboi, Elizabeth A Zeringue, Naohiro Kato, John C Larkin
Endoreplication, a modified cell cycle in which DNA is replicated without subsequent cell division, plays an important but poorly understood role in plant growth and in plant responses to biotic and abiotic stress. The Arabidopsis thaliana SIAMESE (SIM) gene encodes the first identified member of the SIAMESE-RELATED (SMR) family of cyclin-dependent kinase inhibitors. SIM controls endoreplication during trichome development, and sim mutant trichomes divide several times instead of endoreplicating their DNA. The SMR family is defined by several short linear amino acid sequence motifs of largely unknown function, and family members have little sequence similarity to any known protein functional domains...
June 14, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29901106/microwave-hyperthermia-promotes-caspase%C3%A2-3-dependent-apoptosis-and-induces-g2-m-checkpoint-arrest-via-the-atm-pathway-in-non%C3%A2-small-cell-lung-cancer-cells
#2
Yan-Yan Zhao, Qiong Wu, Zhi-Bing Wu, Jing-Jing Zhang, Lu-Cheng Zhu, Yang Yang, Sheng-Lin Ma, Shi-Rong Zhang
Post-operative microwave (MW) hyperthermia has been applied as an important adjuvant therapy to enhance the efficacy of traditional cancer treatment. A better understanding of the molecular mechanisms of MW hyperthermia may provide guided and further information on clinical hyperthermia treatment. In this study, we examined the effects of MW hyperthermia on non‑small cell lung carcinoma (NSCLC) cells in vitro, as well as the underlying mechanisms. In order to mimic clinical treatment, we developed special MW heating equipment for this study...
June 13, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29895527/the-role-of-gsk3-and-its-reversal-with-gsk3-antagonism-in-everolimus-resistance
#3
Elke Tatjana Aristizabal Prada, Gerald Spoettl, Julian Maurer, Michael Lauseker, Eva Koziolek, Jörg Schrader, Ashley B Grossman, Karel Pacak, Felix Beuschlein, Christoph J Auernhammer, Svenja Nölting
Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis. The mTORC1 inhibitor everolimus has been approved for the treatment of advanced NETs. However, the regular development of resistance to everolimus limits its clinical efficacy. We established two independent everolimus-resistant panNET (BON1) cell lines (BON1 RR1, BON1 RR2) to find potential mechanisms of resistance. After 24 weeks of permanent exposure to 10 nM everolimus, BON1 RR1 and BON1 RR2 showed stable resistance with cellular survival rates of 96...
June 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29870118/plasmacytoid-dendritic-cell-heterogeneity-is-defined-by-cxcl10-expression-following-tlr7-stimulation
#4
Casper Marsman, Fanny Lafouresse, Yang Liao, Tracey M Baldwin, Lisa A Mielke, Yifang Hu, Matthias Mack, Paul J Hertzog, Carolyn A de Graaf, Wei Shi, Joanna R Groom
Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the down-stream effectors of type I IFN signaling that amplify autoimmune responses. Here we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation conventional type 1 and type 2 DCs (cDC1 and cDC2 respectively) uniformly upregulate CXCL10...
June 5, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29865033/tpx2-promotes-cell-proliferation-and-migration-via-plk1-in-oc
#5
Shuyun Ma, Xuan Rong, Fei Gao, Yang Yang, Lin Wei
BACKGROUND: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated proteinrequired for mitosis and spindle assembly. It has been revealed that TPX2 is overexpressedin various human cancers and promotes cancer progression. METHODS: The expression of TPX2 was examined in ovarian cancer (OC) tissues and by Western blotting, quantitative real-time reverse transcription PCR (qRT-PCR) and immunohistochemistry. The effects of TPX2 on proliferation and migration of two OC cell lines SKOV3and RMG1 were analyzed using the methylthiazol tetrazolium (MTT) assay, flow cytometry and transwell assay...
May 25, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29802302/anti-influenza-effect-and-action-mechanisms-of-the-chemical-constituent-gallocatechin-7-gallate-from-pithecellobium-clypearia-benth
#6
Chao Li, Lv-Jie Xu, Wen-Wen Lian, Xiao-Cong Pang, Hao Jia, Ai-Lin Liu, Guan-Hua Du
Host cdc2-like kinase 1 (CLK1) is responsible for the alternative splicing of the influenza virus M2 gene during influenza virus infection and replication that has been recognized as a potential anti-influenza virus target. In this study, we showed that gallocatechin-7-gallate (J10688), a novel CLK1 inhibitor isolated from Pithecellobium clypearia Benth, exerted potent anti-influenza virus activity in vivo and in vitro. ICR mice were intranasally infected with a lethal dose of H1N1. Administration of J10688 (30 mg·kg- 1 ·d-1 , iv, for 5 days) significantly increased the survival rate of the H1N1-infected mice to 91...
May 25, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29800601/porcine-epidemic-diarrhea-virus-through-p53-dependent-pathway-causes-cell-cycle-arrest-in-the-g0-g1-phase
#7
Pei Sun, Haoyang Wu, Jiali Huang, Ying Xu, Feng Yang, Qi Zhang, Xingang Xu
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest...
May 22, 2018: Virus Research
https://www.readbyqxmd.com/read/29783721/azd1775-increases-sensitivity-to-olaparib-and-gemcitabine-in-cancer-cells-with-p53-mutations
#8
Xiangbing Meng, Jianling Bi, Yujun Li, Shujie Yang, Yuping Zhang, Mary Li, Haitao Liu, Yiyang Li, Megan E Mcdonald, Kristina W Thiel, Kuo-Kuang Wen, Xinhao Wang, Meng Wu, Kimberly K Leslie
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function...
May 19, 2018: Cancers
https://www.readbyqxmd.com/read/29778921/goat-boule-isoforms-identification-mrna-expression-in-testis-and-functional-study-and-promoter-methylation-profiles
#9
Xiaoyan Zhang, Shuai Yu, Qing Yang, Ke Wang, Sihuan Zhang, Chuanying Pan, Hailong Yan, Ruihua Dang, Chuzhao Lei, Hong Chen, Xianyong Lan
A conserved gene in meiosis, the Boule gene is involved in meiosis and spermatogenesis. The deletion of this gene in males blocks meiosis and results in infertility. Alternative splicing variants of the Boule gene have been identified in humans, bovines, and bats, but in dairy goats remains unknown. This study was therefore to detect splicing variants of the goat Boule gene and explore their potential roles in meiosis. Three isoforms, denoted as Boule-a, Boule-b, and Boule-c, were identified in the testes of goats using real-time PCR (RT-PCR) and cloning sequencing...
May 12, 2018: Theriogenology
https://www.readbyqxmd.com/read/29773584/mechanisms-in-endocrinology-cell-cycle-regulation-in-adrenocortical-carcinoma
#10
Sofia Pereira, Mariana P Monteiro, Isabelle Bourdeau, Andre Lacroix, Duarte Pignatelli
Adrenocortical carcinomas are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers...
May 17, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29769742/modified-citrus-pectin-inhibited-bladder-tumor-growth-through-downregulation-of-galectin-3
#11
Tian Fang, Dan-Dan Liu, He-Ming Ning, Dan Liu, Jing-Ya Sun, Xiao-Jing Huang, Yu Dong, Mei-Yu Geng, Shi-Feng Yun, Jun Yan, Rui-Min Huang
Modified citrus pectin (MCP) is a carbohydrate enriched complex, which has been implicated in cancer treatment and prevention. However, the effects of MCP on urinary bladder cancer (UBC) are unknown. In this study, MCP was first tested in T24 and J82 human UBC cells and showed the inhibition of cell viability by the sulforhodamine B (SRB) assay. The MCP-treated UBC cells exhibited G2 /M phase arrest with the decrease of Cyclin B1 and phosphorylated Cdc2. Caspase-3 was also activated, leading to the cleavage of Caspase-3 and PARP...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29769258/anti-tumor-efficacy-of-a-novel-clk-inhibitor-via-targeting-rna-splicing-and-myc-dependent-vulnerability
#12
Kenichi Iwai, Masahiro Yaguchi, Kazuho Nishimura, Yukiko Yamamoto, Toshiya Tamura, Daisuke Nakata, Ryo Dairiki, Yoichi Kawakita, Ryo Mizojiri, Yoshiteru Ito, Moriteru Asano, Hironobu Maezaki, Yusuke Nakayama, Misato Kaishima, Kozo Hayashi, Mika Teratani, Shuichi Miyakawa, Misa Iwatani, Maki Miyamoto, Michael G Klein, Wes Lane, Gyorgy Snell, Richard Tjhen, Xingyue He, Sai Pulukuri, Toshiyuki Nomura
The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025...
May 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29757976/fatty-acid-%C3%AE-oxidation-is-essential-in-leptin-mediated-oocytes-maturation-of-yellow-catfish-pelteobagrus-fulvidraco
#13
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755453/clec10a-is-a-specific-marker-for-human-cd1c-dendritic-cells-and-enhances-their-toll-like-receptor-7-8-induced-cytokine-secretion
#14
Lukas Heger, Silke Balk, Jennifer J Lühr, Gordon F Heidkamp, Christian H K Lehmann, Lukas Hatscher, Ariawan Purbojo, Arndt Hartmann, Fayna Garcia-Martin, Shin-Ichiro Nishimura, Robert Cesnjevar, Falk Nimmerjahn, Diana Dudziak
Dendritic cells (DCs) are major players for the induction of immune responses. Apart from plasmacytoid DCs (pDCs), human DCs can be categorized into two types of conventional DCs: CD141+ DCs (cDC1) and CD1c+ DCs (cDC2). Defining uniquely expressed surface markers on human immune cells is not only important for the identification of DC subpopulations but also a prerequisite for harnessing the DC subset-specific potential in immunomodulatory approaches, such as antibody-mediated antigen targeting. Although others identified CLEC9A as a specific endocytic receptor for CD141+ DCs, such a receptor for CD1c+ DCs has not been discovered, yet...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754473/actin-dysfunction-induces-cell-cycle-delay-at-g2-m-with-sustained-erk-and-rsk-activation-in-imr-90-normal-human-fibroblasts
#15
Deepmala Shrestha, Daeun Choi, Kiwon Song
The actin cytoskeleton plays a key role in the entry of mitosis as well as in cytokinesis. In a previous study, we showed that actin disruption delays mitotic entry at G2/M by sustained activation of extracellular signal-related kinase 1/2 (ERK1/2) in primary cells but not in transformed cancer cell lines. Here, we examined the mechanism of cell cycle delay at G2/M by actin dysfunction in IMR-90 normal human fibroblasts. We observed that de-polymerization of actin with cytochalasin D (CD) constitutively activated ribosomal S6 kinase (RSK) and induced inhibitory phosphorylation of Cdc2 (Tyr 15) in IMR-90 cells...
May 4, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29752300/intramyocardial-angiogenetic-stem-cells-and-epicardial-erythropoietin-save-the-acute-ischemic-heart
#16
Christian Klopsch, Anna Skorska, Marion Ludwig, Heiko Lemcke, Gabriela Maass, Ralf Gaebel, Martin Beyer, Cornelia Lux, Anita Toelk, Karina Müller, Christian Maschmeier, Sarah Rohde, Petra Mela, Brigitte Müller-Hilke, Stefan Jockenhoevel, Brigitte Vollmar, Robert Jaster, Robert David, Gustav Steinhoff
Ischemic heart failure still displays the highest mortality. An early boost of intracardiac regenerative key mechanisms and angiogenetic niche signaling in cardiac mesenchymal stem cells (MSCs) could improve myocardial infarction (MI) healing. Epicardial erythropoietin (EPO, 300U kg-1 ) was compared with intraperitoneal and intramyocardial EPO treatments after acute MI in rats (n=156). Real-time PCR and confocal microscopy revealed epicardial EPO treatment enhanced intracardiac regenerative key indicators (SDF-1, CXCR-4, CD34, Bcl-2, Cyclin D1, Cdc2, MMP2), induced TGF-β/WNT signaling in intramyocardial MSC niches through direct activation of AKT, upregulations of upstream signals FOS and Fzd7 and augmented intracardiac mesenchymal proliferation 24 hours after MI...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29734760/kaempferol-induces-g2-m-cell-cycle-arrest-via-checkpoint-kinase-2-and-promotes-apoptosis-via-death-receptors-in-human-ovarian-carcinoma-a2780-cp70-cells
#17
Ying Gao, Junfeng Yin, Gary O Rankin, Yi Charlie Chen
Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells...
May 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29731906/expression-level-of-cdc2-gene-in-osteosarcoma-and-its-clinical-significance
#18
Gang Hou, Biying Chen, Wenbin Xu, Huiqing Zhao, Kaihua Liu, Hui Yao
The aim of the present study was to investigate the expression of cell division cycle gene 2 ( CDC2 ) in osteosarcoma tissues and its clinical significance. Specimens of cancer tissues, paracancerous tissues and serum from 47 patients hospitalized at the Department of Orthopedics at The Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) from January, 2010 to January, 2015 and serum from 35 normal subjects were collected. The expression of CDC2 mRNA was evaluated using quantitative polymerase chain reaction (RT-PCR) and the relationship between CDC2 protein expression and clinical features of patients with osteosarcoma was analyzed...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29726984/immune-cell-census-in-murine-atherosclerosis-cytometry-by-time-of-flight-illuminates-vascular-myeloid-cell-diversity
#19
Jennifer E Cole, Inhye Park, David Ahern, Christina Kassiteridi, Dina Danso Abeam, Michael Goddard, Patricia Green, Pasquale Maffia, Claudia Monaco
Aims: Atherosclerosis is characterised by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis. Methods and Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks...
May 2, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29723265/molecular-structures-of-cdc2-like-kinases-in-complex-with-a-new-inhibitor-chemotype
#20
Anne Walter, Apirat Chaikuad, Renate Helmer, Nadège Loaëc, Lutz Preu, Ingo Ott, Stefan Knapp, Laurent Meijer, Conrad Kunick
Cdc2-like kinases (CLKs) represent a family of serine-threonine kinases involved in the regulation of splicing by phosphorylation of SR-proteins and other splicing factors. Although compounds acting against CLKs have been described, only a few show selectivity against dual-specificity tyrosine phosphorylation regulated-kinases (DYRKs). We here report a novel CLK inhibitor family based on a 6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one core scaffold. Within the series, 3-(3-chlorophenyl)-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (KuWal151) was identified as inhibitor of CLK1, CLK2 and CLK4 with a high selectivity margin towards DYRK kinases...
2018: PloS One
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