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G1/S transition

Anja Göder, Claudia Emmerich, Teodora Nikolova, Nicole Kiweler, Maria Schreiber, Toni Kühl, Diana Imhof, Markus Christmann, Thorsten Heinzel, Günter Schneider, Oliver H Krämer
Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show that the histone deacetylases HDAC1/HDAC2 sustain the phosphorylation of the checkpoint kinases ATM, CHK1 and CHK2, activity of the cell cycle gatekeeper kinases WEE1 and CDK1, and induction of the tumour suppressor p53 in response to stalled DNA replication. Consequently, HDAC inhibition upon replicative stress promotes mitotic catastrophe. Mechanistically, HDAC1 and HDAC2 suppress the expression of PPP2R3A/PR130, a regulatory subunit of the trimeric serine/threonine phosphatase 2 (PP2A)...
February 22, 2018: Nature Communications
Pedro G Santiago-Cardona, Jaileene Pérez-Morales, Jonathan González-Flores
The retinoblastoma tumor suppressor protein (pRb) is a preeminent tumor suppressor that acts as a cell cycle repressor, specifically as an inhibitor of the G1-S transition of the cell cycle . pRb is a phosphoprotein whose function is repressed by extensive phosphorylation in several key residues, and therefore, pRb's phosphorylation status has become a surrogate for pRb activity. In particular, hyperphosphorylation of pRb has been associated with pathological states such as cancer, and therefore, assessing pRb's phosphorylation status is increasingly gaining diagnostic and prognostic value, may be used to inform therapeutic decisions, and is also an important tool for the cancer biologists seeking an understanding of the molecular etiology of cancer...
2018: Methods in Molecular Biology
Annika K Weimer, Juliana L Matos, Nidhi Sharma, Farah Patell, James A H Murray, Walter Dewitte, Dominique C Bergmann
Plants, with cells fixed in place by rigid walls, often utilize spatial and temporally distinct cell division programs to organize and maintain organs. This leads to the question of how developmental regulators interact with the cell cycle machinery to link cell division events with particular developmental trajectories. In Arabidopsis leaves, the development of stomata, 2-celled epidermal valves that mediate plant-atmosphere gas exchange, relies on a series of oriented stem-cell-like asymmetric divisions followed by a single symmetric division...
February 21, 2018: Development
Yuqing Shen, John William Sherman, Xuyong Chen, Ruoning Wang
From unicellular to multicellular organisms, cell cycle progression is tightly coupled to biosynthetic and bioenergetic demands. Accumulating evidence has demonstrated the G1/S phase transition as a key checkpoint where cells respond to their metabolic status and commit to replicating the genome. However, the mechanism underlying the coordination of metabolism and the G2/M phase transition in mammalian cells remains unclear. Here we show that the activation of AMP-activated protein kinase (AMPK), a highly conserved cellular energy sensor, significantly delays mitosis entry...
February 21, 2018: Journal of Biological Chemistry
Matthew Lowe, Jacob Lage, Ellen Paatela, Dane Munson, Reilly Hostager, Ce Yuan, Nobuko Katoku-Kikyo, Mercedes Ruiz-Estevez, Yoko Asakura, James Staats, Mulan Qahar, Michaela Lohman, Atsushi Asakura, Nobuaki Kikyo
Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion...
February 20, 2018: Cell Reports
Frank S Heldt, Alexis R Barr, Sam Cooper, Chris Bakal, Béla Novák
Human cells that suffer mild DNA damage can enter a reversible state of growth arrest known as quiescence. This decision to temporarily exit the cell cycle is essential to prevent the propagation of mutations, and most cancer cells harbor defects in the underlying control system. Here we present a mechanistic mathematical model to study the proliferation-quiescence decision in nontransformed human cells. We show that two bistable switches, the restriction point (RP) and the G1/S transition, mediate this decision by integrating DNA damage and mitogen signals...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
L Ottria, V Candotto, F Cura, L Baggi, C Arcuri, M Nardone, R M Gaudio, R Gatto, F Spadari, F Carinci
In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains uncertain...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Fanfan Yi, Yugui Hao, Xiaoyi Chong, Wei Zhong
The aim of the present study was to measure the expression of microRNA (miRNA)-506-3p in the peripheral blood of patients with hypertension and to determine the biological functions and mechanisms of action of miR-506-3p. A total of 61 patients with primary hypertension were included in the present study. Peripheral blood was collected from all patients, as well as 31 healthy subjects who were included in a control group. The expression of miR-506-3p in peripheral blood was determined by reverse transcription-quantitative polymerase chain reaction...
March 2018: Experimental and Therapeutic Medicine
Qiao-Li Lv, Hui-Ting Zhu, Xiao-Hua Cheng, Hong-Mi Li, Hong-Hao Zhou, Shu-Hui Chen
Emerging studies show that dysregulated miRNAs are implicated in tumorigenesis and progression of various cancers. MiRNA-320c, an important member of miRNA-320 family, was characterized as a new candidate miRNA that suppressed the development of colorectal cancer and bladder cancer. However, the function of miRNA-320c in human glioma remained unclear. Here, we found that miRNA-320c was significantly down-regulated in glioma tissues and cell lines in contrast with normal brain tissues, being tightly related to clinical stage of glioma by qRT-PCR...
February 10, 2018: Brain Research Bulletin
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
Gongbiao Lu, Lin Du, Yi Guo, Baohua Xing, Jishou Lu, Yanchun Wei
The aim of the current study was to investigate the expression and role of microRNA (miR)-1271 in the pathogenesis of osteosarcoma, and the associated underlying mechanisms. Tissue samples from 45 patients with osteosarcoma were collected, while the 143B, MG-63 and U-2 OS osteosarcoma cell lines were also cultured. The expression levels of miR-1271 in the tissues and cells were detected with reverse transcription-quantitative polymerase chain reaction, and 143B osteosarcoma cells were subjected to miR-1271 manipulation...
February 2018: Experimental and Therapeutic Medicine
Xuedong Zhang, Yakui Zhang, Yong Mao, Xinlong Ma
Introduction: Osteosarcoma is a malignant primary bone cancer and is lethal to children and adolescents. Recently, the dysregulation of long noncoding RNAs (lncRNAs) has been shown in various types of cancers. Aim: The present study aimed to examine the role of the lncRNA prostate cancer-associated transcript 1 (PCAT1) in osteosarcoma progression. Materials and methods: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time polymerase chain reaction...
2018: OncoTargets and Therapy
Enguang Rong, Jiaxiang Hu, Chenghuai Yang, Hualan Chen, Zeng Wang, Xiaojuan Liu, Wenjie Liu, Chang Lu, Penghua He, Xiaoxue Wang, Xiaoyun Chen, Jinhua Liu, Ning Li, Yinhua Huang
Mammalian interferon-induced proteins with tetratricopeptide repeats (IFITs) play important roles in many cellular processes and host innate immune response to viruses. However, the functions of IFIT proteins in birds are largely unknown. Here, we first describe that the only one avian IFIT protein is orthologous to ancestor of mammalian IFITs. We find that the predicted structure of duck AvIFIT protein is similar to that of human IFIT5. We also find that duck AvIFIT protein shows antiviral activity to a broad range of specific RNA and DNA viruses like mammalian IFIT proteins...
February 8, 2018: Developmental and Comparative Immunology
Lakmini Kumari Senavirathna, Chaoqun Huang, Xiaoyun Yang, Maria Cristina Munteanu, Roshini Sathiaseelan, Dao Xu, Craig A Henke, Lin Liu
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation...
February 9, 2018: Scientific Reports
Li Liu, Na Si, YiCong Ma, DongYu Ge, Xue Yu, AngRan Fan, Xu Wang, JingHong Hu, Peng Wei, Long Ma, ZiWei Chen, Qian Zhang, CuiLing Feng
BACKGROUND Anti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells. MATERIAL AND METHODS BGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARg agonist (RGZ), RGZ+GW9662...
February 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yulin Bi, Lu Xu, Lingling Qiu, Shasha Wang, Xiangping Liu, Yani Zhang, Yang Chen, Yang Zhang, Qi Xu, Guobin Chang, Guohong Chen
Chicken reticuloendotheliosis virus (REV) causes the atrophy of immune organs and immuno-suppression. The pathogenic mechanisms of REV are poorly understood. The aim of this study was to use RNA sequencing to analyse the effect of REV on immunity and cell proliferation in chicken lymphocytes from peripheral blood in vitro. Overall, 2977 differentially expressed genes (DEGs) were examined from cells between infected with REV or no; 56 DEGs related to cell proliferation and 130 DEGs related to immunity were identified...
2018: Frontiers in Physiology
Osama Garwain, Kaitlyn Valla, Suzanne Scarlata
Cells have developed lineage-specific mechanisms to control proliferation and drive morphologic changes upon differentiation. A hallmark of differentiation is the assembly of signaling molecules that transduce extracellular signals, such as the production of the G protein-regulated enzyme phospholipase Cβ (PLCβ), which generates calcium signals from sensory stimuli. We found that in most cancerous cell lines there is positive correlation between PLCβ1 levels and cell proliferation. In cells of neuronal lineage, however, reducing PLCβ1 levels increases the rate of proliferation...
January 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Da-Peng Yun, Yu-Qi Wang, De-Long Meng, Yuan-Yuan Ji, Ju-Xiang Chen, Hong-Yan Chen, Da-Ru Lu
Glioma is the most aggressive and malignant primary brain tumor in adults. In the present study, we identified a vital oncoprotein, capping actin protein, gelsolin-like (CapG), and investigated its roles in the prognosis, proliferation and metastasis in glioma. The mRNA and protein levels of CapG were significantly increased in human glioma, and higher CapG expression was an independent prognostic factor for predicting unfavorable prognosis. The expression level of CapG was found to be associated with several common molecular features of glioblastoma (GBM; WHO grade IV glioma) in The Cancer Genome Atlas (TCGA) cohort...
January 22, 2018: Oncology Reports
Minghui Liu, Hongyu Liu, Jun Chen
An uncontrolled cell cycle is an obvious marker of tumor cells. The G1‑S phase is an important restriction point in the normal cell cycle, but in cancer cells the restriction function is reduced, leading to uncontrolled cell proliferation. Two cyclin‑dependent kinases (CDKs), CDK4 and CDK6, play a crucial role in the G1‑S phase transition. Inhibitors of CDK4/6 are presently the subjects of numerous studies, and PD 0332991, an inhibitor of CDK4/6, has been used to treat hormone receptor (HR)‑positive, advanced‑stage breast cancer...
January 19, 2018: Oncology Reports
Jin Huang, Carl J Mousley, Louis Dacquay, Nairita Maitra, Guillaume Drin, Chong He, Neale D Ridgway, Ashutosh Tripathi, Michael Kennedy, Brian K Kennedy, Wenshe Liu, Kristin Baetz, Michael Polymenis, Vytas A Bankaitis
Kes1/Osh4 is a member of the conserved, but functionally enigmatic, oxysterol binding protein-related protein (ORP) superfamily that inhibits phosphatidylinositol transfer protein (Sec14)-dependent membrane trafficking through the trans-Golgi (TGN)/endosomal network. We now report that Kes1, and select other ORPs, execute cell-cycle control activities as functionally non-redundant inhibitors of the G1/S transition when cells confront nutrient-poor environments and promote replicative aging. Kes1-dependent cell-cycle regulation requires the Greatwall/MASTL kinase ortholog Rim15, and is opposed by Sec14 activity in a mechanism independent of Kes1/Sec14 bulk membrane-trafficking functions...
January 26, 2018: Developmental Cell
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