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G1/S transition

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https://www.readbyqxmd.com/read/29026085/ezh2-enables-germinal-centre-formation-through-epigenetic-silencing-of-cdkn1a-and-an-rb-e2f1-feedback-loop
#1
Wendy Béguelin, Martín A Rivas, María T Calvo Fernández, Matt Teater, Alberto Purwada, David Redmond, Hao Shen, Matt F Challman, Olivier Elemento, Ankur Singh, Ari M Melnick
The EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21(Cip1)). Deletion of Cdkn1a rescues the GC reaction in Ezh2 (-/-) mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a (-/-) Ezh2 (-/-) mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29021622/the-circadian-transcriptome-of-marine-fish-sparus-aurata-larvae-reveals-highly-synchronized-biological-processes-at-the-whole-organism-level
#2
M Yúfera, E Perera, J A Mata-Sotres, J Calduch-Giner, G Martínez-Rodríguez, J Pérez-Sánchez
The regulation of circadian gene expression remains largely unknown in farmed fish larvae. In this study, a high-density oligonucleotide microarray was used to examine the daily expression of 13,939 unique genes in whole gilthead sea bream (Sparus aurata) larvae with fast growth potentiality. Up to 2,229 genes were differentially expressed, and the first two components of Principal Component Analysis explained more than 81% of the total variance. Clustering analysis of differentially expressed genes identified 4 major clusters that were triggered sequentially, with a maximum expression at 0 h, 3 h, 9-15 h and 18-21 h zeitgeber time...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993193/%C3%AE-lipoic-acid-inhibits-human-lung-cancer-cell-proliferation-through-grb2-mediated-egfr-downregulation
#3
Lan Yang, Ya Wen, Guoqing Lv, Yuntao Lin, Junlong Tang, Jingxiao Lu, Manqiao Zhang, Wen Liu, Xiaojuan Sun
BACKGROUND: Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. METHODS: The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28992327/the-steady-state-level-of-cdk4-protein-is-regulated-by-antagonistic-actions-between-paqr4-and-skp2-and-involved-in-tumorigenesis
#4
Lin Wang, Rui Zhang, Xue You, Huanhuan Zhang, Siying Wei, Tingting Cheng, Qianqian Cao, Zhenzhen Wang, Yan Chen
CDK4 is crucial for G1-to-S transition of cell cycle. It is well established that ubiquitin-mediated degradations of CDK inhibitors and cyclins are pivotal for the timely and unidirectional progression of cell cycle. However, how CDK4 itself is modulated by ubiquitin-mediated degradation has been elusive. Here we report that the steady-state level of CDK4 is controlled by PAQR4, a member of the progestin and adipoQ receptor family, and SKP2, an E3 ubiquitin ligase. Knockdown of PAQR4 leads to reduction of cell proliferation, accompanied by reduced protein level of CDK4...
September 12, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28986587/the-drinking-water-contaminant-dibromoacetonitrile-delays-g1-s-transition-and-suppresses-chk1-activation-at-broken-replication-forks
#5
Thomas Caspari, James Dyer, Nathalie Fenner, Christian Dunn, Chris Freeman
Chlorination of drinking water protects humans from water-born pathogens, but it also produces low concentrations of dibromoacetonitrile (DBAN), a common disinfectant by-product found in many water supply systems. DBAN is not mutagenic but causes DNA breaks and elevates sister chromatid exchange in mammalian cells. The WHO issued guidelines for DBAN after it was linked with cancer of the liver and stomach in rodents. How this haloacetonitrile promotes malignant cell transformation is unknown. Using fission yeast as a model, we report here that DBAN delays G1-S transition...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978134/samhd1-acetylation-enhances-its-deoxynucleotide-triphosphohydrolase-activity-and-promotes-cancer-cell-proliferation
#6
Eun Ji Lee, Ji Hae Seo, Ji-Hyeon Park, Tam Thuy Lu Vo, Sunho An, Sung-Jin Bae, Hoang Le, Hye Shin Lee, Hee-Jun Wee, Danbi Lee, Young-Hwa Chung, Jeong A Kim, Myoung-Kuk Jang, Soo Hyung Ryu, Ensil Yu, Se Hwan Jang, Zee Yong Park, Kyu-Won Kim
SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28946006/phosphorylation-of-transcriptional-regulators-in-the-retinoblastoma-protein-pathway-by-ul97-the-viral-cyclin-dependent-kinase-encoded-by-human-cytomegalovirus
#7
Satoko Iwahori, Robert F Kalejta
Human cytomegalovirus (HCMV) encodes a viral cyclin-dependent kinase (v-CDK), the UL97 protein. UL97 phosphorylates Rb, p107 and p130, thereby inactivating all three retinoblastoma (Rb) family members. Rb proteins function through regulating the activity of transcription factors to which they bind. Therefore, we examined whether the UL97-mediated regulation of the Rb tumor suppressors also extended to their binding partners. We observed that UL97 phosphorylates LIN52, a component of p107- and p130-assembled transcriptionally repressive DREAM complexes that control transcription during the G0/G1 phases, and the Rb-associated E2F3 protein that activates transcription through G1 and S phases...
September 22, 2017: Virology
https://www.readbyqxmd.com/read/28945228/erk-dependent-il-6-autocrine-signaling-mediates-adaptive-resistance-to-pan-pi3k-inhibitor-bkm120-in-head-and-neck-squamous-cell-carcinoma
#8
M R Yun, H M Choi, H N Kang, Yw Lee, H-S Joo, D H Kim, H R Kim, M H Hong, S O Yoon, B C Cho
Hyperactivation of phosphatidylinositol 3-kinase (PI3K) pathway occurs frequently in head and neck squamous cell carcinoma (HNSCC). However, clinical outcomes of targeting the PI3K pathway have been underwhelming. In present study, we investigated the resistant mechanisms and potential combination therapeutic strategy to overcome adaptive resistance to PI3K inhibitor in HNSCC. Treatment of NVP-BKM120, a pan-PI3K inhibitor, led to upregulation of interleukin-6 (IL-6) and subsequent activation of either extracellular signal-regulated kinase (ERK) or signal transducers and activators of transcription 3 (STAT3), causing modest antitumor effects on the growth of HNSCC cells...
September 25, 2017: Oncogene
https://www.readbyqxmd.com/read/28938565/lncrna-afap1-as1-promotes-growth-and-metastasis-of-cholangiocarcinoma-cells
#9
Xiuhui Shi, Hang Zhang, Min Wang, Xiaodong Xu, Yan Zhao, Ruizhi He, Min Zhang, Min Zhou, Xu Li, Feng Peng, Chengjian Shi, Ming Shen, Xin Wang, Xingjun Guo, Renyi Qin
We investigated the role of actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) lncRNA in promoting cholangiocarcinoma (CCA). qRT-PCR analysis of patient samples showed that AFAP1-AS1 expression was higher in CCA tumors than matched adjacent non-tumor tissue. AFAP1-AS1 levels were also higher in CCA cell lines (HuCCT1 and TFK-1) than a normal biliary epithelium cell line (HIBEpic). AFAP1-AS1 knockdown in CCA cell lines using shAFAP1-AS1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28933981/tfpi2as1-a-novel-lncrna-that-inhibits-cell-proliferation-and-migration-in-lung-cancer
#10
Shenglan Gao, Ziying Lin, Chunyan Li, Yahong Wang, Lawei Yang, Baoan Zou, Jie Chen, Jianwen Li, Zeqing Song, Gang Liu
Accumulating evidence demonstrates that a series of differentially expressed lncRNAs is important in tumorigenesis. However, the function of many of the lncRNAs in lung cancer remains elusive. In the present study, we used microarray analysis to identify lncRNAs that are dysregulated in non-small-cell lung cancer (NSCLC) as compared with normal tissues. Among the dysregulated lncRNAs, we identified TFPI2AS1, an antisense transcript of the tumor suppressor TFPI2 (tissue factor pathway inhibitor 2). TFPI2AS1 was shown to be markedly upregulated in NSCLC patient tumors as compared to paired non-tumor samples...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28931595/cell-cycle-transitions-a-common-role-for-stoichiometric-inhibitors
#11
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
https://www.readbyqxmd.com/read/28927264/comparative-interactomes-of-vrk1-and-vrk3-with-their-distinct-roles-in-the-cell-cycle-of-liver-cancer
#12
Namgyu Lee, Dae-Kyum Kim, Seung Hyun Han, Hye Guk Ryu, Sung Jin Park, Kyong-Tai Kim, Kwan Yong Choi
Vaccinia-related kinase 1 (VRK1) and VRK3 are members of the VRK family of serine/threonine kinases and are principally localized in the nucleus. Despite the crucial roles of VRK1/VRK3 in physiology and disease, the molecular and functional interactions of VRK1/VRK3 are poorly understood. Here, we identified over 200 unreported VRK1/VRK3-interacting candidate proteins by affinity purification and LC-MS/MS. The networks of VRK1 and VRK3 interactomes were found to be associated with important biological processes such as the cell cycle, DNA repair, chromatin assembly, and RNA processing...
September 30, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28924058/localization-of-cdc7-protein-kinase-during-dna-replication-in-saccharomyces-cerevisiae
#13
Daniel Rossbach, D Suzi Bryan, Jay R Hesselberth, Robert Sclafani
DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations...
September 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28924038/passive-dna-demethylation-preferentially-up-regulates-pluripotency-related-genes-and-facilitates-the-generation-of-induced-pluripotent-stem-cells
#14
Songwei He, Hao Sun, Lilong Lin, Yixin Zhang, Jinlong Chen, Lining Liang, Yuan Li, Mengdan Zhang, Xiao Yang, Xiaoshan Wang, Fuhui Wang, Feiyan Zhu, Jiekai Chen, Duanqing Pei, Hui Zheng
A high proliferation rate has been observed to facilitate somatic cell reprogramming, but the pathways that connect proliferation and reprogramming have not been reported. DNA methyltransferase 1 (DNMT1) methylates hemimethylated CpG sites produced during S phase and maintains stable inheritance of DNA methylation. Impairing this process results in passive DNA demethylation. In this study, we show that the cell proliferation rate positively correlated with the expression of Dnmt1 in G1 phase. In addition, as determined by whole genome bisulfate sequencing and high-performance liquid chromatography, global DNA methylation of mouse embryonic fibroblasts (MEFs) was significantly higher in G1 phase than in G2/M phase...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923602/cell-wall-mannoprotein-of-candida-albicans-induces-cell-cycle-alternation-and-inhibits-apoptosis-of-hacat-cells-via-nf-%C3%AE%C2%BAb-signal-pathway
#15
Yang Han, Hang-Hang Jiang, Yu-Jing Zhang, Xing-Jia Hao, Yu-Zhe Sun, Rui-Qun Qi, Hong-Duo Chen, Xing-Hua Gao
Candida albicans (C. albicans) is a commensal organism in human and a well-known dimorphic opportunistic pathogenic fungus. Though plenty of researches on the pathogenesis of C. albicans have been performed, the mechanism is not fully understood. The cell wall components of C. albicans have been documented to play important roles in its pathogenic processes. To further study the infectious mechanism of C. albicans, we investigated the potential functional role of its cell wall mannoprotein in cell cycle and apoptosis of HaCaT cells...
October 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28918036/therapeutic-suppression-of-mir-4261-attenuates-colorectal-cancer-by-targeting-mcc
#16
Guanming Jiao, Qi Huang, Muren Hu, Xuchun Liang, Fuchen Li, Chunling Lan, Wencheng Fu, Yu An, Bin Xu, Jinzhe Zhou, Junjie Xiao
The mutated in colorectal cancer (MCC) gene is an important colorectal tumor suppressor gene, although few studies have reported the microRNA(s) that could directly target MCC in colorectal cancer. Here, we used microRNA (miRNA) target prediction algorithms, and previously reported microarray data in human colorectal cancer found that only miR-4261 was predicted by all three databases to directly target MCC. Based on specimens from our own cohort of colorectal cancer patients, we further demonstrated that miR-4261 was overexpressed in colorectal cancer...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917019/the-trend-toward-minimally-invasive-complex-abdominal-wall-reconstruction-is-it-worth-it
#17
Igor Belyansky, Adam S Weltz, Udai S Sibia, Justin J Turcotte, Haley Taylor, H Reza Zahiri, T Robert Turner, Adrian Park
BACKGROUND: Open abdominal wall reconstruction (AWR) was previously one of the only methods available to treat complex ventral hernias. We set out to identify the impact of laparoscopy and robotics on our AWR program by performing an economic analysis before and after the institution of minimally invasive AWR. METHODS: We retrospectively reviewed inpatient hospital costs and economic factors for a consecutive series of 104 AWR cases that utilized separation of components technique (57 open, 38 laparoscopic, 9 robotic)...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28905990/the-mtor-kinase-inhibitor-everolimus-synergistically-enhances-the-anti-tumor-effect-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-pls-123-on-mantle-cell-lymphoma
#18
Jiao Li, Xiaogan Wang, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Zhengying Pan, Ning Ding, Yuqin Song, Jun Zhu
Mantle cell lymphoma (MCL) is an aggressive and incurable malignant disease. Despite of general chemotherapy, relapse and mortality are common, highlighting the need for the development of novel targeted drugs or combination of therapeutic regimens. Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901378/androgen-independent-lncap-cells-are-a-subline-of-lncap-cells-with-a-more-aggressive-phenotype-and-androgen-suppresses-their-growth-by-inducing-cell-cycle-arrest-at-the-g1%C3%A2-phase
#19
Pan Yu, Xiuzhi Duan, Yue Cheng, Chunhua Liu, Yuhua Chen, Weiwei Liu, Binbin Yin, Xuchu Wang, Zhihua Tao
Androgen deprivation therapy (ADT, surgical or chemical castration) is the mainstay treatment for metastatic prostate cancer (PCa); however, patients ineluctably relapse despite extremely low androgen levels. This evolution of PCa indicates its lethal progression. In this study, to mimic the traits of clinical PCa progression in vitro, we investigated the alterations in the cell biological characteristics in androgen-independent LNCaP cells (LNCaP-AI cells) compared with LNCaP cells. We also examined the effects of androgen on LNCaP and LNCaP-AI cell proliferation, androgen receptor (AR) expression and prostate-specific antigen (PSA) secretion...
September 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28890348/mir-362-3p-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-atherosclerosis-by-targeting-adamts1
#20
Meiling Li, Qing Liu, Jiayan Lei, Xiaoliang Wang, Xiaoyun Chen, Yanhui Ding
Atherosclerosis is a progressive condition of the large arteries that can cause coronary artery disease (CAD). Growing amounts of evidence have indicated that microRNAs (miRNAs, miRs) can be used as diagnostic biomarkers in many cellular processes associated with CAD. MiR-362-3p has been implicated in many biological cellular functions. However, little is known about the role of miR-362-3p during atherosclerosis. In the present study, significant downregulation of miR-362-3p was observed in 110 atherosclerotic CAD patients and not in the 84 controls...
November 4, 2017: Biochemical and Biophysical Research Communications
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