The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn-/- mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcnflox/flox). The reintroduction of tumor-associated FLCN mutants (FLCN DF157, FLCN 1-469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and ...
The retinoblastoma protein: Rb) inhibits both cell division and apoptosis, but the mechanism by which Rb alternatively regulates these divergent outcomes remains poorly understood. Cyclin dependent kinases: Cdks) promote cell division by phosphorylating and reversibly inactivating Rb by a hierarchical series of phosphorylation events and sequential conformational changes. The stress-regulated mitogen activated protein kinase: MAPK) p38 also phosphorylates Rb, but it does so in a cell cycle-independent manner that is associated with apoptosis rather than with cell division. Here, we show that p38 phosphorylates Rb by a novel mechanism that is distinct from that of Cdks. p38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates Rb on Ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not Cdks, triggers an interaction between Rb and the human homologue of murine double minute 2: Hdm2), leading to degradation of Rb, release of
Rice (Oryza sativa L.) as a model and crop plant with a sequenced genome offers an outstanding experimental system for discovering and functionally analyzing the major cell cycle control elements in a cereal species. In this study, we identified the core cell cycle genes in the rice genome through a hidden Markov model search and multiple alignments supported with the use of short protein sequence probes. In total we present 55 rice putative cell cycle genes with locus identity, chromosomal location, approximate chromosome position and EST accession number. These cell cycle genes include nine cyclin dependent-kinase (CDK) genes, 27 cyclin genes, one CKS gene, two RBR genes, nine E2F/DP/DEL genes, six KRP genes, and one WEE gene. We also provide characteristic protein sequence signatures encoded by CDK and cyclin gene variants. Promoter analysis by the FootPrinter program discovered several motifs in the regulatory region of the core cell cycle genes. As a first step towards functional ...
TY - JOUR. T1 - High-resolution timing of cell cycle-regulated gene expression. AU - Rowicka-Kudlicka, Malgorzata. AU - Kudlicki, Andrzej. AU - Tu, Benjamin P.. AU - Otwinowski, Zbyszek. PY - 2007/10/23. Y1 - 2007/10/23. N2 - The eukaryotic cell division cycle depends on an intricate sequence of transcriptional events. Using an algorithm based on maximum-entropy deconvolution, and expression data from a highly synchronized yeast culture, we have timed the peaks of expression of transcriptionally regulated cell cycle genes to an accuracy of 2 min (≈1% of the cell cycle time). The set of 1,129 cell cycle-regulated genes was identified by a comprehensive analysis encompassing all available cell cycle yeast data sets. Our results reveal distinct subphases of the cell cycle undetectable by morphological observation, as well as the precise timeline of macromolecular complex assembly during key cell cycle events.. AB - The eukaryotic cell division cycle depends on an intricate sequence of ...
Retinoids have antiproliferative effects in human breast cancer cells and share some characteristics with antiestrogens, although the molecular targets involved have yet to be identified in either case. Using T-47D human breast cancer cells, we compared the effects of retinoic acid (RA) and the antiestrogen ICI 164384 on cell cycle phase distribution and the expression of genes with known functions in cell cycle control. Both RA and ICI 164384 inhibited cell cycle progression in G1 phase, but the RA effect was delayed by 16 h. This delay in action was also seen with 9-cis RA and other retinoids. Administration of 17 beta-estradiol abolished the effects of ICI 164384 but was without effect in RA-treated cells. Antiestrogen treatment caused a rapid inhibition of c-myc and cyclin D1 gene expression and reduced Cdk2 activity by more than 50% at 24 h. RA, however, did not affect c-myc or cyclin D1 gene expression, nor did it significantly change the mRNA or protein levels of cyclins D3 or E or cyclin
Combinations of gemcitabine and trabectedin exert modest synergistic cytotoxic effects on two pancreatic cancer cell lines. Here, systems pharmacodynamic (PD) models that integrate cellular response data and extend a prototype model framework were developed to characterize dynamic changes in cell cycle phase of cancer cell subpopulations in response to gemcitabine and trabectedin as single agents and in combination. Extensive experimental data were obtained for two pancreatic cancer cell lines (MiaPaCa-2 and BxPC-3), including cell proliferation rates over 0-120 h of drug exposure, and the fraction of cells in different cell cycle phases or apoptosis. Cell cycle analysis demonstrated that gemcitabine induced cell cycle arrest in S phase, and trabectedin induced transient cell cycle arrest in S phase that progressed to G2/M phase. Over time, cells in the control group accumulated in G0/G1 phase. Systems cell cycle models were developed based on observed mechanisms and were used to characterize both cell
The cell cycle includes 4 main phases: Gap 1 (G1), DNA replication (S), Gap 2 (G2), and mitosis (M). Tight regulation of the transition between these phases halts cell cycle progression if a phase is not properly completed. For example, the G2-M DNA damage checkpoint ensures the fidelity of DNA replication, and arrests the cell cycle to allow time for replication error correction and DNA damage repair. Cell cycle progression is regulated by the cyclic rise and fall of kinase expression, and their interaction with, and action on, their cyclin targets. Cell cycle dysregulation commonly occurs during oncogenesis, and tumor cells often do not arrest the cell cycle when normally required. Key genes that regulate cell cycle progression and checkpoints encode cullins, cyclins, and cyclin-dependent kinases and their inhibitors. Other cell cycle regulatory genes include apoptosis regulators and DNA damage sensors ...
Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.. Terminally differentiated neurons are unable to reenter the cell cycle. Aberrant cell cycle activation provokes neuronal cell death, whereas cell cycle inhibition elevates neuronal survival. However, the molecular mechanism regulating the cell cycle and cell death in mature neurons remains elusive. Here we show that SRPK2, a protein kinase specific for the serine/arginine (SR) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin D1. Akt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. We find that SRPK2 is phosphorylated in ischemia-attacked brain, correlating with the ...
TY - CHAP. T1 - Myocardial regeneration via cell cycle activation. AU - LaFontant, Pascal J.. AU - Field, Loren J.. PY - 2007/1/1. Y1 - 2007/1/1. N2 - Introduction During development, increases in heart size results as a consequence of the differentiation and proliferation of cardiomyocytes, neurons, interstitial cells, and components of the vasculature. At birth, cardiomyocytes undergo a gradual transition from hyperplastic to hypertrophic growth, such that subsequent increases in myocardial mass result largely from increased myocyte size rather than increased number. In contrast, the other cell types present in the heart retain the ability to proliferate. Consequently, in adults, although cardiomyocytes constitute approximately 90% of the mass of the heart, they constitute less than 20% of the total number of cells present.. AB - Introduction During development, increases in heart size results as a consequence of the differentiation and proliferation of cardiomyocytes, neurons, interstitial ...
The Cell Cycle Ontology ( http://www.CellCycleOntology.org ) is an application ontology that automatically captures and integrates detailed knowledge on the cell cycle process. Cell Cycle Ontology is enabled by semantic web technologies, and is accessible via the web for browsing, visualizing, advanced querying, and computational reasoning. Cell Cycle Ontology facilitates a detailed analysis of cell cycle-related molecular network components. Through querying and automated reasoning, it may provide new hypotheses to help steer a systems biology approach to biological network building.
TY - JOUR. T1 - Double blockade of cell cycle at G1-S transition and M phase by 3-iodoacetamido benzoyl ethyl ester, a new type of tubulin ligand. AU - Jiang, Jian Dong. AU - Denner, Larry. AU - Ling, Yi He. AU - Li, Jian Nong. AU - Davis, Ashley. AU - Wang, Yue. AU - Li, Yan. AU - Roboz, Julia. AU - Wang, Long Gui. AU - Perez-Soler, Roman. AU - Marcelli, Marco. AU - Bekesi, George. AU - Holland, James F.. PY - 2002. Y1 - 2002. N2 - 3-Iodoacetamido benzoyl ethyl ester (3-IAABE) is a new compound synthesized in our laboratory. The primary action of 3-IAABE is to inhibit microtubule assembly by interacting with -SH groups on tubulin. In contrast to other known microtubule disrupters, 3-IAABE caused a double blockade in the cell cycle at G1-S transition and in M phase. The blockade was determined by cell cycle analysis and chromosome distribution. Kinase activities of cyclin E and cyclin-dependent kinase 2 responsible for the G1-S transition were increased, as were the activities of mitotic cyclin ...
Pluripotency and the capability for self-renewal are essential characteristics of human embryonic stem cells (hESCs), which hold great potential as a cellular source for tissue replacement. Short cell cycle (15-16 h) compared to somatic cells is another property of hESCs. Efficient synchronization of hESCs at different cell cycle stages is important to elucidate the mechanistic link between cell cycle regulation and cell fate decision. This protocol describes how to establish synchronization of hESCs at different cell cycle stages.
TY - JOUR. T1 - A cell cycle study of the effects of Con A on synchronized mouse embryo fibroblasts. T2 - Arrest and dissociation between uptake of thymidine and DNA synthesis. AU - Mallucci, L.. AU - Dunn, M.. AU - Wells, V.. AU - Delia, D.. PY - 1980. Y1 - 1980. N2 - We have examined the effects of 50 μg ml-1 of Con A added to synchronized mouse embryo fibroblasts at different times during the cell cycle. We found that Con A caused arrest of growth not solely by preventing G1-G0 cells from entering the S-phase but also by exerting a G2 block. We also found that Con A, which prevented commencement of S-phase, did not arrest cells already in S from reaching the G2 stage but inhibited the S-phase associated process of thymidine uptake. The inhibition was greater when the Con A receptors were extensively clustered.. AB - We have examined the effects of 50 μg ml-1 of Con A added to synchronized mouse embryo fibroblasts at different times during the cell cycle. We found that Con A caused arrest of ...
During the cell division cycle of the yeast Saccharomyces cerevisiae, the G1-to-S transition depends upon the activation of two transcription factors (SBF and MBF), which are responsible for the cell cycle-regulated expression of more than 200 genes. Bck2 becomes essential in the absence of Cln3, the most upstream activator of this transcriptional program. Here we have used a genome-wide approach to elucidate the targets of Bck2. Our data indicate that Bck2 activates a selection of cell cycle-regulated genes from all cell cycle stages. In contrast, Cln3 activates only G1/S phase genes. Furthermore, Bck2 activates many genes independently of Swi6, the common component of SBF and MBF. Comparison of Bck2 targets with those of other transcription factors suggests that, in addition to SBF and MBF, Bck2 may elicit gene expression via Ste12 and Mcm1. We propose that Bck2 activates its targets by a mechanism fundamentally different from that of Cln3, and that it may be a necessary cofactor for the full ...
Time-course microarray experiments have been widely used to identify cell cycle regulated genes. However, the method is not effective for lowly expressed genes and is sensitive to experimental conditions. To complement microarray experiments, we propose a computational method to predict cell cycle regulated genes based on their genomic features - transcription factor binding and motif profiles. Through integrating gene-expression data with ChIP-chip binding and putative binding sites of transcription factors, our method shows high accuracy in discriminating yeast cell cycle regulated genes from non-cell cycle regulated ones. We predict 211 novel cell cycle regulated genes. Our model rediscovers the main cell cycle transcription factors and provides new insights into the regulatory mechanisms. The model also reveals a regulatory circuit mediated by a number of key cell cycle regulators. Our model suggests that the periodical pattern of cell cycle genes is largely coded in their promoter regions, which
TY - JOUR. T1 - Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis. AU - Li, Fuhai. AU - Zhou, Xiaobo. AU - Ma, Jinwen. AU - Wong, Stephen T C. PY - 2010/1. Y1 - 2010/1. N2 - Automated cell segmentation and tracking are critical for quantitative analysis of cell cycle behavior using time-lapse fluorescence microscopy. However, the complex, dynamic cell cycle behavior poses new challenges to the existing image segmentation and tracking methods. This paper presents a fully automated tracking method for quantitative cell cycle analysis. In the proposed tracking method, we introduce a neighboring graph to characterize the spatial distribution of neighboring nuclei, and a novel dissimilarity measure is designed based on the spatial distribution, nuclei morphological appearance, migration, and intensity information. Then, we employ the integer programming and division matching strategy, together with the novel dissimilarity measure, to track cell nuclei. We ...
PURPOSE The cell cycle progression test is a validated molecular assay that assesses prostate cancer specific disease progression and mortality risk when combined with clinicopathological parameters. We present the results from PROCEDE-1000, a large, prospective registry designed to evaluate the impact of the cell cycle progression test on shared treatment decision making for patients newly diagnosed with prostate cancer. MATERIALS AND METHODS Untreated patients with newly diagnosed prostate adenocarcinoma were enrolled in the study and the cell cycle progression test was performed on the initial prostate biopsy tissue. A set of 4 sequential surveys tracked changes relative to initial therapy recommendations (before cell cycle progression) based on clinicopathological parameters following physician review of the cell cycle progression test result, physician/patient review of the cell cycle progression test results and a minimum of 3 months of clinical followup (actual treatment). RESULTS Of the 1
TY - JOUR. T1 - Association of cell cycle expression of Ia-like antigenic determinants on normal human multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells with regulation in vitro by acidic isoferritins. AU - Lu, L.. AU - Broxmeyer, H. E.. AU - Meyers, P. A.. AU - Moore, M. A.. AU - Thaler, H. T.. PY - 1983. Y1 - 1983. N2 - An association has been established between human Ia-like antigenic determinants, expression during DNA synthesis on multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells, and the regulatory action of acidic isoferritins in vitro. Treatment of human bone marrow cells with monoclonal anti-Ia (NE1-011) plus complement inhibited colony formation of CFU-GEMM and BFU-E by 50%-70%. Reduction of colonies was similar whether bone marrow cells were exposed to anti-Ia plus complement, high specific activity tritiated thymidine (3HTdr), or acidic isoferritins. No further decrease was apparent with 3HTdr or acidic isoferritins after Ia-antigen+ CFU-GEMM or BFU-E ...
Cell Growth and Reproduction Study Guide The Cell Cycle Study Guide Vocabulary - Cell Cycle, Mitosis, Cytokinesis 1. How did the G1 and G2 stages get their
Successful progression through the cell cycle requires spatial and temporal regulation of gene transcript levels and the number, positions and condensation levels of chromosomes. Here we present a high resolution survey of genome interactions in Schizosaccharomyces pombe using synchronized cells to investigate cell cycle dependent changes in genome organization and transcription. Cell cycle dependent interactions were captured between and within S. pombe chromosomes. Known features of genome organization (e.g. the clustering of telomeres and retrotransposon long terminal repeats (LTRs)) were observed throughout the cell cycle. There were clear correlations between transcript levels and chromosomal interactions between genes, consistent with a role for interactions in transcriptional regulation at specific stages of the cell cycle. In silico reconstructions of the chromosome organization within the S. pombe nuclei were made by polymer modeling. These models suggest that groups of genes with high ...
Geminiviruses are small DNA viruses that use plant replication machinery to amplify their genomes. Microarray analysis of the Arabidopsis (Arabidopsis thaliana) transcriptome in response to cabbage leaf curl virus (CaLCuV) infection uncovered 5,365 genes (false discovery rate ,0.005) differentially expressed in infected rosette leaves at 12 d postinoculation. Data mining revealed that CaLCuV triggers a pathogen response via the salicylic acid pathway and induces expression of genes involved in programmed cell death, genotoxic stress, and DNA repair. CaLCuV also altered expression of cell cycle-associated genes, preferentially activating genes expressed during S and G2 and inhibiting genes active in G1 and M. A limited set of core cell cycle genes associated with cell cycle reentry, late G1, S, and early G2 had increased RNA levels, while core cell cycle genes linked to early G1 and late G2 had reduced transcripts. Fluorescence-activated cell sorting of nuclei from infected leaves revealed a ...
The cell cycle is central to understanding fundamental biology of Leishmania, a group of human-infective protozoan parasites. Leishmania have two main life cycle morphologies: the intracellular amastigote in the mammalian host and the promastigote in the fly. We have produced the first comprehensive and quantitative description of a Leishmania promastigote cell cycle taking a morphometric approach to position any cell within the cell cycle based on its length and DNA content. We describe timings of cell cycle phases and rates of morphological changes; kinetoplast and nucleus S phase, division and position, cell body growth and morphology changes, flagellum growth and basal body duplication. We have shown that Leishmania mexicana undergoes large changes in morphology through the cell cycle and that the wide range of morphologies present in cultures during exponential growth represent different cell cycle stages. We also show promastigote flagellum growth occurs over multiple cell cycles. There are clear
Live fast, die soon: cell cycle progression and lifespan in yeast cells - Our understanding of lifespan has benefited enormously from the study of a simple model, the yeast Saccharomyces cerevisiae. Although a unicellular organism, yeasts undergo many of the processes directly related with aging that to some extent are conserved in mammalian cells. Nutrient-limiting conditions have been involved in lifespan extension, especially in the case of caloric restriction, which also has a direct impact on cell cycle progression. In fact, other environmental stresses (osmotic, oxidative) that interfere with normal cell cycle progression also influence the lifespan of cells, indicating a relationship between lifespan and cell cycle control. In the present review we compile and discuss new findings related to how cell cycle progression is regulated by other nutrients. We centred this review on the analysis of phosphate, also give some attention to nitrogen, and the impact of these nutrients on lifespan...
Distinct patterns of histone methylation during human cell cycle progression are described. Histone H4 methyltransferase activity is cell cycle-regulated, consistent with increased H4 Lys 20 methylation at mitosis. This increase closely follows the cell cycle-regulated expression of the H4 Lys 20 methyltransferase, PR-Set7. Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation were inversely correlated to transient H4 Lys 16 acetylation in early S-phase. These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted (Rice, 2002). To determine histone methyltransferase activity during the human cell cycle, HeLa cells were arrested by treatment with thymidine followed by mimosine. Every 2.5 h following release from the G1 arrest, synchronized cells were isolated for analysis, and the cell cycle phase was determined by ...
Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi-scale model (a ...
A recent in-depth view of cell cycle regulation and cancer has provided novel samples of research at the Frontiers of Science. However, the number of foremost revealing information about both the topics has been derived from the intersection of these two fields.1-5 This review intends to introduce the basics of the cell cycle and its regulation at different checkpoints in relation to cancer. Cancer is broadly a result of unchecked cell multiplication due to abnormal activity of varied cell cycle proteins; therefore, cell cycle regulators are considered attractive targets in cancer therapy. Many cancers are uniquely linked with these proteins and are therefore selectively sensitive to their inhibition.6 After a long run of research on the physiological functions of cell cycle proteins and their relevance for cancer, these data recently got converted into the first approved cancer therapeutics, targeting the regulator of cell cycle.7 Here, we are reviewing the role of cell cycle proteins in ...
NADPH oxidase 2 (Nox2)-derived oxidative stress and redox-signalling have been found to play an important role in hyperglycaemia-induced endothelial dysfunction in diabetes. Acetate (NaA) is a member of the short chain fatty acids (SCFA) family which acts through G-protein coupled receptor 43 (GPCR43) to exert anti-inflammatory effects and to increase insulin sensitivity. However, its action in endothelial cells remains unknown. In this study we investigated the effects of NaA and GPCR43 on high glucose (30 mM, 24 h)-induced Nox2 activation and endothelial cell cycle progression using human pulmonary microvascular endothelial cells (HPMECs). Compared to control cells, high glucose increased significantly i) Nox2-derived superoxide production (48.5±12.6%) as detected by both lucigenin (5 µM)-chemiluminescence and DHE fluorescence; ii) expression of cyclin D, A and E and cell cycle progression from G0/G1 to S and G2/M phases and iii) cell apoptosis (30.66±8.3%) (all p,0.05). These high-glucose ...
The neocortex is patterned in layers of neurons that are generated in an orderly sequence during development. This correlation between cell birthday and laminar fate prompted an examination of how neuronal phenotypes are determined in the developing cortex. At various times after labeling with [3H]thymidine, embryonic progenitor cells were transplanted into older host brains. The laminar fate of transplanted neurons correlates with the position of their progenitors in the cell cycle at the time of transplantation. Daughters of cells transplanted in S-phase migrate to layer 2/3, as do host neurons. Progenitors transplanted later in the cell cycle, however, produce daughters that are committed to their normal, deep-layer fates. Thus, environmental factors are important determinants of laminar fate, but embryonic progenitors undergo cyclical changes in their ability to respond to such cues. ...
TY - JOUR. T1 - ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1. AU - Han, J.. AU - Kim, Y. L.. AU - Lee, K. W.. AU - Her, N. G.. AU - Ha, T. K.. AU - Yoon, S.. AU - Jeong, S. I.. AU - Lee, J. H.. AU - Kang, M. J.. AU - Lee, M. G.. AU - Ryu, B. K.. AU - Baik, J. H.. AU - Chi, S. G.. PY - 2013/8. Y1 - 2013/8. N2 - ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and ...
For many organisms, the first goal of embryogenesis is to accumulate a large cell population to accommodate gastrulation. To achieve this quickly, embryos employ specialized cell cycles called cleavages that consist of continuous rounds of DNA replication and division. Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical cell cycles. Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle progression. After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. Cell cycles lengthen, gap phases appear and checkpoint function is acquired. At the same time, the nearly quiescent zygotic genome is activated and transcriptional activity dramatically increases. This dissertation describes how these simultaneous MBT events are regulated. Chapter 2 addresses how
CYCD3;1 expression in Arabidopsis is associated with proliferating tissues such as meristems and developing leaves but not with differentiated tissues. Constitutive overexpression of CYCD3;1 increases CYCD3;1-associated kinase activity and reduces the proportion of cells in the G1-phase of the cell cycle. Moreover, CYCD3;1 overexpression leads to striking alterations in development. Leaf architecture in overexpressing plants is altered radically, with a failure to develop distinct spongy and palisade mesophyll layers. Associated with this, we observe hyperproliferation of leaf cells; in particular, the epidermis consists of large numbers of small, incompletely differentiated polygonal cells. Endoreduplication, a marker for differentiated cells that have exited from the mitotic cell cycle, is inhibited strongly in CYCD3;1-overexpressing plants. Transcript analysis reveals an activation of putative compensatory mechanisms upon CYCD3;1 overexpression or subsequent cell cycle activation. These ...
Cell proliferation is essential for many key processes that occur during development including organogenesis, tissue renewal and germline formation. (Bartkova et al., 1997; Clurman and Roberts, 1995; Pines, 1995; Sandhu and Slingerland, 2000). Therefore, the timing of cell division and differentiation must be precisely coordinated with signals that specify morphogenesis, patterning and growth in a temporal, positional and cell type-specific manner (reviewed by Vidwans and Su, 2001). This coordination is executed through regulating both positive and negative regulatory components of the basal cell cycle machinery.. The cell cycle machinery is well conserved among eukaryotes and complex mechanisms ensure that cell cycle progression occurs in a timely and precise sequence. Cyclin-dependent kinases (Cdks) drive progression through the different cell cycle phases (reviewed by Nigg, 2001). In yeasts, these catalytic subunits are regulated through their association with stage-specific cyclin regulatory ...
Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the cell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established. We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade. ...
TY - JOUR. T1 - Rapamycin blocks IL-2-driven T cell cycle progression while preserving T cell survival. AU - Gonzalez, Juana. AU - Harris, Tom. AU - Childs, Geoffrey. AU - Prystowsky, Michael B.. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Effective cellular immune responses require increases in antigen-specific T lymphocytes; IL-2 drives antigen-stimulated T cell proliferation and is largely responsible for the increases observed. We used microarrays containing ∼9000 mouse cDNAs to study IL-2-induced gene expression. IL-2 induces the expression of genes that regulate cell cycle progression, control cell survival, and increase synthetic and metabolic processes during proliferation. IL-2 also suppresses expression of genes that block cell cycle progression and promote cell death. Rapamycin inhibits IL-2-driven proliferation by downregulating the expression of genes required for key processes required for cell cycle progression. Rapamycin also preserves cell survival by keeping intact the IL-2-induced ...
TY - JOUR. T1 - Cell-size dependent progression of the cell cycle creates homeostasis and flexibility of plant cell size. AU - Jones, Angharad R.. AU - Forero-Vargas, Manuel. AU - Withers, Simon P.. AU - Smith, Richard S.. AU - Traas, Jan. AU - Dewitte, Walter. AU - Murray, James A.H.. PY - 2017/1/1. Y1 - 2017/1/1. N2 - © The Author(s) 2017. Mean cell size at division is generally constant for specific conditions and cell types, but the mechanisms coupling cell growth and cell cycle control with cell size regulation are poorly understood in intact tissues. Here we show that the continuously dividing fields of cells within the shoot apical meristem of Arabidopsis show dynamic regulation of mean cell size dependent on developmental stage, genotype and environmental signals. We show cell size at division and cell cycle length is effectively predicted using a two-stage cell cycle model linking cell growth and two sequential cyclin dependent kinase (CDK) activities, and experimental results concur ...
Cell proliferation is the main driving force for plant growth. Although genome sequence analysis revealed a high number of cell cycle genes in plants, little is known about the molecular complexes steering cell division. In a targeted proteomics approach, we mapped the core complex machinery at the heart of the Arabidopsis thaliana cell cycle control. Besides a central regulatory network of core complexes, we distinguished a peripheral network that links the core machinery to up- and downstream pathways. Over 100 new candidate cell cycle proteins were predicted and an in-depth biological interpretation demonstrated the hypothesis-generating power of the interaction data. The data set provided a comprehensive view on heterodimeric cyclin-dependent kinase (CDK)cyclin complexes in plants. For the first time, inhibitory proteins of plant-specific B-type CDKs were discovered and the anaphase-promoting complex was characterized and extended. Important conclusions were that mitotic A- and B-type ...
The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle protein 20 (CDC20), a recombinase RAD51, and serine-threonine protein kinase CHEK1 as effective targets for breast cancer therapy, and demonstrated their therapeutic potential in breast cancer MDA-MB-435, MDA-MB-231 and MCF7 cells with respect to another well-studied cell cycle protein, kinesin spindle protein. We also explored the efficacy of dicer-substrate siRNA
In recent years, increasing research has focused on the relationship between cytokines and tumorigenesis. It has been suggested that cytokines may be a new therapeutic option for tumors (16-20). In our experiments, we demonstrated that IFN-λ1 inhibited the growth of gastric carcinoma cells in a concentration-dependent manner. These data suggest that IFN-λ1 may be a potential antitumor agent for the treatment of gastric cancer.. Impaired apoptotic induction and dysregulated cell cycle progression are important factors in cancer development. Accordingly, inhibition of cell cycle regulation is particularly useful in the treatment of cancer. In our in vitro study, we demonstrated the apoptosis-inducing effects of IFN-λ1 in gastric carcinoma cells using PI cell cycle analysis, Annexin V and PI staining as well as activated caspase-3. Our study showed that IFN-λ1 induced G1 phase arrest and apoptosis in the gastric carcinoma cells.. Experimental evidence suggests that apoptosis can be mediated by ...
Tumor cells stably transfected with fluorescent proteins enable scientists to visualize many important aspects of cancer in real time at the single cell level. For example, transfected tumor cells have been visualized either through surgically created chronic-transparent windows or directly through the opened skin of living animals [29]. This intravital imaging provides a powerful tool for observing cancer initiation and progression and evaluating the efficacy of candidate cancer drugs in vivo. On the other hand, assays using tumor cells grown in culture provide reliable information about cancer mechanisms, and are amenable to automated high-throughput screening [16-20]. Using a modified fluorescent indicator of cell cycle progression (Fucci2) and cultured immortalized cells, we investigated the mechanism(s) by which anticancer drugs modulate the cell cycle. While population analysis provided statistical data, time-lapse high-resolution imaging analysis allowed us to explore the processes of ...
Proper DNA replication and well-timed cell cycle progression are vital to the normal functioning of a cell. Precise coordination between these mechanisms constituent proteins ensures their processivity while safeguarding against DNA damage. The Ctf4 protein is a central member of the replication fork and links the replicative MCM helicase and polymerase [alpha]-primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC). This investigation represents the first phenotypic analysis of the function of the Ctf4 protein within a multicellular organism model. We show that Ctf4 interacts with Polymerase [alpha], MCM2, Psf1, and Psf2. We also demonstrate that knockdown of this central replication fork component via a GAL4-UAS RNAi system results in a lower frequency of mitosis due to an S-phase delay, endoreplication defects, as well as mitotic bridging in early embryonic development ...
It is widely believed that the cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus because during cell cycle progression in mammalian cells it interacts with molecules that are important regulators of cellular proliferation, suck as the retinoblastoma tumour suppressor gene product (pRb), p107, cyclins and cyclin-dependent kinases. Thus, pRb, which negatively regulates early cell cycle progression and is frequently mutated in tumour cells, and the Rb-related protein p107, bind to and repress the transcriptional activity of DRTF1/E2F. Viral oncoproteins, such as adenovirus E1a and SV40 large T antigen, overcome such repression by sequestering pRb and p107 and in so doing are likely to activate genes regulated by DRTF1/E2F, such as cdc2, c-myc and DHFR. Two sequence-specific DNA binding proteins, E2F-1 and DP-1, which bind to the E2F site, contain a small region of similarity. The functional relationship between them has, however, been unclear. We report
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cells progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA ...
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cells progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA ...
is a supervised approach for PrEdicting cell cycle phase in a COntinuum using single-cell RNA sequencing data. The R package provides functions to build training dataset and also functions to use existing training data to predict cell cycle on a continuum.. Our work demonstrated that peco is able to predict continuous cell cylce phase using a small set of cylcic genes: CDK1, UBE2C, TOP2A, HISTH1E, and HISTH1C (identified as cell cycle marker genes in studies of yeast (Spellman et al., 1998) and HeLa cells (Whitfield et al., 2002)).. Below we provide two use cases. Vignette 1 shows how to use the built-training dataset to predict continuous cell cycle. Vignette 2 shows how to make a training datast and build a predictor using training data.. Users can also view the vigenettes via ...
Video articles in JoVE about g2 phase include Cell Cycle Analysis in the C. elegans Germline with the Thymidine Analog EdU, Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols, Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM), Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis.
The centromeric histone CENP-A is incorporated at different cell cycle phases during somatic mitosis, meiosis I and meiosis II in Drosophila melanogaster.
What is Cell Cycle Gene? Definition of Cell Cycle Gene. Cell Cycle Gene FAQ. Learn more about Cell Cycle Gene. Cell Cycle Gene facts.
Cell Cycle Activity Worksheet Fresh Lifescitrc Cells Alive Mitosis Phase Worksheet one of Free Worksheets - Free, printable main idea worksheets to develop strong reading comprehension skills ideas, to explore this Cell Cycle Activity Worksheet Fresh Lifescitrc Cells Alive Mitosis Phase Worksheet idea you can browse by and . We hope your happy with this Cell Cycle Activity Worksheet Fresh Lifescitrc Cells Alive Mitosis Phase Worksheet idea. You can download and please share this Cell Cycle Activity Worksheet Fresh Lifescitrc Cells Alive Mitosis Phase Worksheet ideas to your friends and family via your social media account. Back to Cell Cycle Activity Worksheet. ...
Abstract: Modern sugarcane is an unusually complex heteroploid crop, and its genome comprises two or three subgenomes. To reduce the complexity of sugarcane genome research, the ploidy level and number of chromosomes can be reduced using flow chromosome sorting. However, a cell cycle synchronization (CCS) protocol for Saccharum spp. is needed that maximizes the accumulation of metaphase chromosomes. For flow cytometry analysis in this study, we optimized the lysis buffer, hydroxyurea(HU) concentration, HU treatment time and recovery time for sugarcane. We determined the mitotic index by microscopic observation and calculation. We found that WPB buffer was superior to other buffers for preparation of sugarcane nuclei suspensions. The optimal HU treatment was 2 mM for 18 h at 25 °C, 28 °C and 30 °C. Higher recovery treatment temperatures were associated with shorter recovery times (3.5 h, 2.5 h and 1.5 h at 25 °C, 28 °C and 30 °C, respectively). The optimal conditions for treatment with the ...
Genistein, an isoflavone, is a specific inhibitor of tyrosine kinase and topoisomerase II. However, its effect on cell growth is unknown. Therefore, we examined the effects of genistein on cell growth and cell cycle progression and compared its effects with other flavonoids. Genistein inhibited in a dose-dependent manner the growth of HGC-27 cells derived from human gastric cancer. Flow-cytometric analysis showed that genistein almost completely arrested the cell cycle progression at G2-M. This effect was reversible when genistein was removed from the culture medium. In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1. Consistent with the flow-cytometric analysis, microscopic observation showed that genistein did not increase the mitotic index, which supposes that genistein may arrest the cell cycle at G2 or early M. These results suggest that the G2-M arrest by genistein is a unique effect among flavonoids.. ...
Successful completion of the cell division cycle is critical for cellular duplication and survival. There are many regulators and checkpoints to ensure the proper cell cycle progression. Disruption of the machinery involved in completion, error correction, or regulation of the cell cycle can be deleterious and may lead to aberrant cell growth or cell death. Thus, it is important to understand not only the basic machinery, but also the underlying choreographed gene expression that underlies that fundamental process. The work presented in this thesis furthers our understanding of the cell cycle in three ways. First, I investigate the cell cycle-regulated transcription factor FOXM1, a gene that has been shown to play a role in the G2 to M phase transition. I show that FOXM1 is cell cycle-regulated in both HeLa and U2OS cells and that, when knocked out in synchronous HeLa cells, results in mis-regulation of select G2/M genes. I also demonstrate that FOXM1 binds to the promoters of many cell ...
Successful completion of the cell division cycle is critical for cellular duplication and survival. There are many regulators and checkpoints to ensure the proper cell cycle progression. Disruption of the machinery involved in completion, error correction, or regulation of the cell cycle can be deleterious and may lead to aberrant cell growth or cell death. Thus, it is important to understand not only the basic machinery, but also the underlying choreographed gene expression that underlies that fundamental process. The work presented in this thesis furthers our understanding of the cell cycle in three ways. First, I investigate the cell cycle-regulated transcription factor FOXM1, a gene that has been shown to play a role in the G2 to M phase transition. I show that FOXM1 is cell cycle-regulated in both HeLa and U2OS cells and that, when knocked out in synchronous HeLa cells, results in mis-regulation of select G2/M genes. I also demonstrate that FOXM1 binds to the promoters of many cell ...
Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers, enter and distribute in cells by energy-dependent pathways1-3. Until now, most studies have shown that nanoparticle properties, such as size4-6 and surface7,8, can affect how cells internalise nanoparticles. Here we show that the different phases of cell growth, which constitute the cell cycle, can also influence nanoparticle uptake. Although cells in different cell cycle phases internalised nanoparticles with similar rates, after 24 hours of uptake the concentration of nanoparticles in the cells is ranked according to the different cell cycle phases: G2/M , S , G0/G1. Nanoparticles were not exported from cells but the internalised nanoparticle concentration is split when the cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle because in a cell population, the internalised nanoparticle dose in each cell varies as the cell cycles ...
The unicellular green alga Chlamydomonas reinhardtii is an ideal model organism for studies of ciliary function and assembly. In assays for biological and biochemical effects of various factors on flagellar structure and function, synchronous culture is advantageous for minimizing variability. Here, we have characterized a method in which 100% synchronization is achieved with respect to flagellar length but not with respect to the cell cycle. The method requires inducing flagellar regeneration by amputation of the entire cell population and limiting regeneration time. This results in a maximally homogeneous distribution of flagellar lengths at 3 h postamputation. We found that time-limiting new protein synthesis during flagellar synchronization limits variability in the unassembled pool of limiting flagellar protein and variability in flagellar length without affecting the range of cell volumes. We also found that long- and short-flagella mutants that regenerate normally require longer and ...
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Carrageenan is a polysaccharide that exists in the cell walls of marine red algae and is widely used in studies concerned with its antitumor and cytotoxic activities [10]. Previous findings show carrageenan as a potential antitumor agent [28-30]. Considering one of the hallmarks of cancer is uncontrolled proliferation, a consequence of the loss of normal cell-cycle control, there has been a. increasing interest in potential anticancer agents that affect the cell-cycles of cancer cells [31]. Thus, in this study we investigated how carrageenan affects tumor cell cycle.. In this study we demonstrated cytotoxic effects of carrageenan towards cell cycle of human cancer cells in HeLa expressing FUCCI probes [24]. Two types of carrageenan, kappa (k-CO) and lambda (λ-CO) carrageenan were used because sulfate contents vary in each type of carrageenan [32]. These sulfated moieties in saccharides are believed to play an important role in manifestation of beneficial bioactivity [33]. Thus cytotoxic ...
Looking for online definition of Cell cycle regulatory protein in the Medical Dictionary? Cell cycle regulatory protein explanation free. What is Cell cycle regulatory protein? Meaning of Cell cycle regulatory protein medical term. What does Cell cycle regulatory protein mean?
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ym.edu.tw.Abstract. Amyloid beta-peptide (Aβ), the neurotoxic component of senile plaques in Alzheimers disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aβs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al., Mol Neurobiol 53(2):793-809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aβ-induced Id1 and SHH contribute to cell cycle reentry leading to apoptosis in neurons. We found that Aβ triggered cell cycle progression in the post-mitotic neurons, as indicated by the increased expression of two G1-phase markers including cyclin D1 and phosphorylated retinoblastoma protein (pRb), two G2-phase markers such as proliferating cell nuclear antigen (PCNA) and incorporation of 5-bromo-2′-deoxyuridine (BrdU) into newly synthesized ...
Cdc14 is an essential phosphatase in yeast but its role in the mammalian cell cycle remains obscure. We report here that Cdc14b-knockout cells display unscheduled induction of multiple cell cycle regulators resulting in early entry into DNA replication and mitosis from quiescence. Cdc14b dephosphorylates Ser5 at the C-terminal domain (CTD) of RNA polymerase II, a major substrate of cyclin-dependent kinases. Lack of Cdc14b results in increased CTD-Ser5 phosphorylation, epigenetic modifications that mark active chromatin, and transcriptional induction of cell cycle regulators. These data suggest a function for mammalian Cdc14 phosphatases in the control of transcription during the cell cycle ...
Second messengers control a wide range of important cellular functions in eukaryotes and prokaryotes. Here we show that cyclic di-GMP, a global bacterial second messenger, promotes cell cycle progression in Caulobacter crescentus by mediating the specific degradation of the replication initiation inhibitor CtrA. During the G1-to-S-phase transition, both CtrA and its cognate protease ClpXP dynamically localize to the old cell pole, where CtrA is rapidly degraded. Sequestration of CtrA to the cell pole depends on PopA, a newly identified cyclic di-GMP effector protein. PopA itself localizes to the cell pole and directs CtrA to this subcellular site via the direct interaction with a mediator protein, RcdA. We present evidence that c-di-GMP regulates CtrA degradation during the cell cycle by controlling the dynamic sequestration of the PopA recruitment factor to the cell pole. Furthermore, we show that cell cycle timing of CtrA degradation relies on converging pathways responsible for substrate and ...
Recent advances in defining the molecular mechanisms of cell cycle control in eukaryotes provide a basis for better understanding the hormonal control of cell proliferation in normal and neoplastic breast epithelium. It is now clear that a number of critical steps in cell cycle progression are controlled by families of serine/threonine kinases, the cdks. These kinases are activated by interactions with various cyclin gene products which form the regulatory subunits of the kinase complexes. Several families of cyclins control cell cycle progression in G1 phase, cyclins C, D and E, or in S, G2 and mitosis, cyclins A and B. Recent studies have defined the expression and regulation of cyclin genes in normal breast epithelial cells and in breast cancer cell lines. Following growth arrest of T-47D breast cancer cells by serum deprivation restimulation with insulin results in sequential induction of cyclin genes. Cyclin D1 mRNA increases within 1 h of mitogenic stimulation and is followed by increased
Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NF kappa B have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NF kappa B and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NF kappa B pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7 wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K ...
Hematopoietic stem cells (HSCs) give rise to all blood populations due to their long-term self-renewal and multipotent differentiation capacities. Because they have to persist throughout an organisms life span, HSCs tightly regulate the balance between proliferation and quiescence. Here, we investigated the role of the transcription factor promyelocytic leukemia zinc finger (plzf) in HSC fate using the Zbtb16(lu/lu)mouse model, which harbors a natural spontaneous mutation that inactivates plzf. Regenerative stress revealed that Zbtb16(lu/lu)HSCs had a lineage-skewing potential from lymphopoiesis toward myelopoiesis, an increase in the long-term-HSC pool, and a decreased repopulation potential. Furthermore, oldplzf-mutant HSCs present an amplified aging phenotype, suggesting that plzf controls age-related pathway. We found that Zbtb16(lu/lu)HSCs harbor a transcriptional signature associated with a loss of stemness and cell cycle deregulation. Lastly, cell cycle analyses revealed an important ...
TY - JOUR. T1 - Cooperation between Different Forms of the Human Papillomavirus Type 1 E4 Protein To Block Cell Cycle Progression and Cellular DNA Synthesis. AU - Knight, G. L.. AU - Grainger, J. R.. AU - Gallimore, P. H.. AU - Roberts, S.. PY - 2004/12/15. Y1 - 2004/12/15. N2 - Posttranslational modification-oligomerization, phosphorylation, and proteolytic cleavage-of the human papillomavirus (HPV) E4 protein occurs as the infected keratinocytes migrate up through the suprabasal wart layers. It has been postulated that these events modify E4 function during the virus life cycle. In HPV type 1 (HPV1)-induced warts, N-terminal sequences are progressively cleaved from the full-length E4 protein (E1∧E4) of 17 kDa to produce a series of polypeptides of 16, 11 and 10 kDa. Here, we have shown that in human keratinocytes, a truncated protein (E4-16K), equivalent to the 16-kDa species, mediated a G2 arrest in the cell cycle that was dependent on a threonine amino acid in a proline-rich domain of the ...
Effects of treatment with serum-free medium and 25-hydroxycholesterol (25-OH) on the cell cycle of simian virus 40-transformed 3T3 fibroblasts, designated SV-3T3 cells, were studied and compared with simultaneous effects on the activity of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and incorporation of [3H]mevalonic acid into cholesterol, Coenzyme Q, and dolichol. The data confirm our previous finding (O. Larsson and A. Zetterberg, Cancer Res., 46: 1233-1239, 1986) that 25-OH inhibits the cell cycle traverse of SV-3T3 cells specifically in early G1. In contrast, treatment with serum-free medium had no effect on cell cycle progression. The effect of 25-OH on the cell cycle traverse was correlated to a substantial decrease in the activity of HMG CoA reductase, whereas there was no change in the rate of [3H]mevalonic acid incorporated into cholesterol, Coenzyme Q, and dolichol. When the cells were exposed to serum-free medium, there was no depression of activity of HMG CoA reductase, and the ...
Ribosome biogenesis and cell cycle are coordinated processes (Du and Stillman, 2001 Bernstein and Baserga, 2004; Fatica and Tollervey, 2002; Li et al., 2009; Strezoska et al., 2002). Mutations in genes encoding factors that are involved in ribosome biogenesis cause defects in ribosomal RNA processing as well as cell cycle arrest. Recent studies with mammalian cell lines have shown that ribosome biogenesis is also linked to tumorgenesis, that is mutation or depletion of ribosomal factors, leads to cancer cell proliferation (Montanaro et al., 2008). The yeast Saccharomyces cerevisiae is a useful model organism for understanding the connections between ribosome biogenesis and cell cycle control. Only a handful of studies have been done and these have mainly focused on different transacting factors involved in ribosome biogenesis; few studies have focused on the roles of r-proteins themselves in linking cell cycle progression and rRNA processing. I wanted to investigate what roles these r-proteins ...
Cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. In Trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go with respect to determining signal transduction pathways. However, it is clear that cell cycle regulation in T. brucei is unusual in many respects. Analyses of trypanosome orthologues of conserved eukaryotic cell cycle regulators have demonstrated divergence of their function in the parasite, and a number of other key regulators are missing from T. brucei. Cell cycle regulation differs in different parasite life cycle stages, and T. brucei appears to use different checkpoint control strategies compared to model
Since the frequencies of various erythroblast subpopulations were unchanged in DKO bone marrow (Figure 2A and B), we next investigated the erythroblast cell cycle. During terminal differentiation, erythroblasts undergo approximately 4-5 rapid cell divisions accompanied by a progressive decrease in cell size, followed by exit from the cell cycle.22 The decrease in erythroblast size during terminal maturation divisions has been attributed to the loss or alteration of the cell size control at the G1-S restriction point leading to the shortening of the G1 phase of the cell cycle without changes to the length of S and G2/M phase.23 To investigate changes in cell cycle time and G1 length in erythroblasts, we measured the length of various cell cycle phases in adult DKO mice bone marrow erythroblasts by cumulative BrdU labeling of bone marrow cells in culture (Figure 2H and I). The cell cycle time (Tc) and the length of S-phase (Ts) were calculated using the Nowakowski method.24 The cell cycle time for ...
Ribosomal protein L4 (RPL4) is a large ribosomal subunit protein that is structurally conserved in all kingdoms of life. This protein is a component of the 90S pre-ribosomal particle that initiates ribosomal assembly on the primary (35S) transcript. Here I show that in vivo repression of Rpl4p synthesis in S. cerevisiae results in severe loss of 60S ribosomal subunits and affects progression of the cell cycle. Analysis of rRNA processing suggests that these effects are associated with a block in the processing of the 27SA3 precursor RNA into 5.8S and 25S rRNA as well as a delay in processing of 35S precursor. More surprisingly, depletion of Rpl4p results in a unique bi-budded phenotype, with multiple cell cycle defects mainly affecting mitotic exit. To further characterize the role of RPL4 in cell cycle progression, I isolated temperature-sensitive L4 mutants. To date I have analyzed one of these mutants. Six hours after a temperature shift of this mutant, cells are uniformly arrested in SG2 ...
TY - JOUR. T1 - RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. AU - Siede, Wolfram. AU - Friedberg, Andrew S.. AU - Friedberg, Errol C.. PY - 1993/9/1. Y1 - 1993/9/1. N2 - Exposure of the yeast Saccharomyces cerevisiae to ultraviolet (UV) light, the UV-mimetic chemical 4-nitroquinoline-1-oxide (4NQO), or γ radiation after release from G1 arrest induced by α factor results in delayed resumption of the cell cycle. As is the case with G2 arrest following ionizing radiation damage [Weinert, T. A. & Hartwell, L. H. (1988) Science 241, 317-322], the normal execution of DNA damage-induced G1 arrest depends on a functional yeast RAD9 gene. We suggest that the RAD9 gene product may interact with cellular components common to the G1/S and G2/M transition points in the cell cycle of this yeast. These observations define a checkpoint in the eukaryotic cell cycle that may facilitate the repair of lesions that are otherwise processed to ...
TY - JOUR. T1 - Clusterin and DNA repair. T2 - A new function in cancer for a key player in apoptosis and cell cycle control. AU - Shannan, B.. AU - Seifert, M.. AU - Boothman, D. A.. AU - Tilgen, W.. AU - Reichrath, J.. PY - 2006/9/1. Y1 - 2006/9/1. N2 - The glycoprotein clusterin (CLU), has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. Both forms are implicated in various cell functions, including DNA repair, cell cycle regulation, and apoptotic cell death. CLU expression has been associated with tumorigenesis and the progression of various malignancies. In response to DNA damage, cell survival can be enhanced by activation of DNA repair mechanisms, while simultaneously stimulating energy-expensive cell cycle checkpoints that delay the cell cycle progression to allow more time for DNA repair. This review summarizes our current understanding of the role of clusterin in DNA repair, apoptosis, and ...
Abstract: Prostate cancer remains a leading cause of death in men despite increased capacity to diagnose at earlier stages. After prostate cancer has become hormone independent which often occurs after hormonal ablation therapies it is difficult to effectively treat. Prostate cancer may arise from mutations and dysregulation of various genes involved in regulation signal transduction (e.g. PTEN Akt etc. ) and the cell cycle (e.g. p53 p21Cip1 p27Kip1 Rb etc. ). This review focuses on the aberrant interactions of signal transduction and cell cycle genes products and how they can contribute to prostate cancer and alter therapeutic effectiveness. Originally published Cell Cycle Vol. 7 No. 12 June 2008 ...
Single cell genomics and proteomics with the combination of innovative three-dimensional (3D) cell culture techniques can open new avenues toward the understanding of intra-tumor heterogeneity. Here, we characterize lung cancer markers using single cell mass cytometry to compare different in vitro cell culturing methods: two-dimensional (2D), carrier-free, or bead-based 3D culturing with in vivo xenografts. Proliferation, viability, and cell cycle phase distribution has been investigated. Gene expression analysis enabled the selection of markers that were overexpressed: TMEM45A, SLC16A3, CD66, SLC2A1, CA9, CD24, or repressed: EGFR either in vivo or in long-term 3D cultures. Additionally, TRA-1-60, pan-keratins, CD326, Galectin-3, and CD274, markers with known clinical significance have been investigated at single cell resolution. The described twelve markers convincingly highlighted a unique pattern reflecting intra-tumor heterogeneity of 3D samples and in vivo A549 lung cancer cells. In 3D systems CA9,
The mammalian BTG/Tob family is a group of proteins with anti-proliferative ability, and there are six members including BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2. Among them, Tob subfamily members, specifically Tob1/Tob and Tob2, have the most extensive C-terminal regions. As previously reported, overexpression of BTG/Tob proteins is associated with the inhibition of G1 to S-phase cell cycle progression and decreased cell proliferation in a variety of cell types. Tob subfamily proteins have similar anti-proliferative effects on cell cycle progression in cultured tumor cells. An important unresolved question is whether or not they have function in rapidly proliferating cells, such as embryonic stem cells (ESCs). Tob1 and Tob2 were expressed ubiquitously in mouse ESCs (mESCs), suggesting a possible role in early embryonic development and mESCs. To address the above question and explore the possible functions of the Tob subfamily in ESCs, we established ESCs from different ...
Biol. and in an affordable, high-throughput manner have constrained DNA damage and repair research on this topic. To resolve this, we developed an inexpensive, high capacity, 96-well plate-compatible alpha particle irradiator capable of delivering adjustable, low mGy/s particle radiation doses in multiple model systems Phthalylsulfacetamide and on the benchtop of a standard laboratory. The system enables Phthalylsulfacetamide monitoring alpha particle effects Phthalylsulfacetamide on DNA damage repair and signalling, genome stability pathways, oxidative stress, cell cycle phase distribution, cell viability and clonogenic survival using numerous microscopy-based and physical techniques. Most importantly, this method is foundational for high-throughput genetic screening and small molecule testing in mammalian and yeast cells. INTRODUCTION Since the discovery of radioactivity more than a century ago, science has made extraordinary progress on understanding the effects of ionizing radiation (IR) on ...
Stem cell self-renewal, commitment and reprogramming rely on a poorly understood coordination of cell cycle progression and execution of cell fate choices. Using existing experimental paradigms, it has not been possible to probe this relationship systematically in live stem cells in vitro or in vivo. Alterations in stem cell cycle kinetics probably occur long before changes in phenotypic markers are apparent and could be used as predictive parameters to reveal changes in stem cell fate. To explore this intriguing concept, we developed a single-cell tracking approach that enables automatic detection of cell cycle phases in live (stem) cells expressing fluorescent ubiquitylation-based cell-cycle indicator (FUCCI) probes. Using this tool, we have identified distinctive changes in lengths and fluorescence intensities of G1 (red fluorescence) and S/G2-M (green) that are associated with self-renewal and differentiation of single murine neural stem/progenitor cells (NSCs) and embryonic stem c
Synchronous cultures of Chlorella, that were obtained with minimum metabolic perturbation by centrifugal selection, reveal that progress through the cell cycle requires no change in the poly(A)+ mRNA population, although changes do occur during nutritional adaptation. Of the abundant soluble proteins, 93% are synthesized continuously through the cell cycle and those that are discontinuous show similar patterns in control cells. The synthesis of proteins is compared with parallel studies of accumulation of enzyme activity and it is shown that there is no discrepancy in their pattern of accumulation when both are studied under the same culture conditions. The eukaryote cell cycle can allow stable relative rates of synthesis of most proteins and balanced rates of accumulation of most enzyme activities. Macromolecule classes differ in their rates of accumulation throughout the cell cycle: total RNA increases linearly, poly(A)+ RNA accumulation is restricted to G1 phase, but total protein ...
TY - JOUR. T1 - Cell cycle dependent oscillatory expression of estrogen receptor-α links Pol II elongation to neoplastic transformation. AU - Vantaggiato, Cristina. AU - Tocchetti, Marta. AU - Cappelletti, Vera. AU - Gurtner, Aymone. AU - Villa, Alessandro. AU - Daidone, Maria Grazia. AU - Piaggio, Giulia. AU - Maggi, Adriana. AU - Ciana, Paolo. PY - 2014/7/1. Y1 - 2014/7/1. N2 - Decades of studies provided a detailed view of the mechanism of estrogen receptor-α (ERα) regulated gene transcription and the physio-pathological relevance of the genetic programs controlled by this receptor in a variety of tissues. However, still limited is our knowledge on the regulation of ERα synthesis. Preliminary observations showed that the expression of ERα is cell cycle regulated. Here, we have demonstrated that a well described polymorphic sequence in the first intron of ERα (PvuII and XbaI) has a key role in regulating the ERα content in cycling cells. We have shown that the RNA Pol II (Pol II) ...
In proliferating cells, the cell cycle consists of four phases. Gap 1 (G1) is the interval between mitosis and DNA replication that is characterized by cell growth. Replication of DNA occurs during the synthesis (S) phase, which is followed by a second gap phase (G2) during which growth and preparation for cell division occurs. Together, these three stages comprise the interphase phase of the cell cycle. Interphase is followed by the mitotic (M) phase. Mitosis and the production of two daughter cells occur in M phase. As the cell cycle controls cell replication and apoptosis, it is essential for the passage through the phases of the cell cycle and related processes to be regulated. Cyclin-dependent kinases (cdks), complexed with various cyclins, regulate the progression through G1-S-G2 phases by triggering DNA replication, transition from phase to phase, and transition into M phase. DNA synthesis occuring in the S phase is essential to passing on genetic information to daughter cells, but loss ...
Over a dozen of the leading scientific investigators in the cell cycle field will gather at the Salk including speakers from the University of Toronto, The Scripps Research Institute, The London Research Institute, The New York University School of Medicine, The Stowers Institute, Stanford University, Dana-Farber Cancer Institute, University of California Berkeley, The Ludwig Institute at UC San Diego, Edinburgh University, Ohio State University, Harvard University and The Sanford Burnham Institute. This symposium has become a labor of love and public service, said Dr. Tony Hunter, Professor, Molecular and Cell Biology Laboratory, Director of the Salk Institute Cancer Center and American Cancer Society Professor. Examining and sharing information about the crucial process of the cell cycle may lend new insights into the identification of biological markers that predict patients responsiveness to chemotherapy drugs and ultimately could lead to the development of new cancer drugs with fewer ...
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BACKGROUND: Receptors belonging to the epidermal growth factor receptor (EGFR) family transfer extracellular signals by homotypic and heterotypic receptor interaction and cross-activation. Cell differentiation, death, and proliferation are regulated via these receptor-tyrosine-kinases. However, the initial mechanisms that lead to signal specificity and diversity, which cause a defined cellular response, are incompletely understood. We investigated the recruitment of receptor complexes in two c-erbB2-overexpressing breast carcinoma cell lines, SK-BR-3 and BT474, after ligand binding and its effects on intracellular signal transduction and cell cycle regulation. METHODS: In order to analyze the coaggregation of receptors on the cell surface induced by specific growth factor treatment, we used the flow cytometric Foerster-type fluorescence resonance energy transfer (FRET) technique. Cell cycle kinetics were monitored flow cytometrically via the anti-BrdU technique and acitivation of intracellular ...
TY - JOUR. T1 - Cell cycle analysis using flow cytometry. AU - Gray, J. W.. AU - Dolbeare, F.. AU - Pallavicini, M. G.. AU - Beisker, W.. AU - Waldman, F.. PY - 1986/1/1. Y1 - 1986/1/1. N2 - This manuscript reviews the utility of flow cytometry for the study of cell proliferation. The applications of univariate DNA distribution analysis to cytokinetic studies of asynchronous and perturbed cell populations are discussed briefly. The newly developed technique for simultaneous flow cytometric measurement of cellular DNA content and amount of incorporated bromodeoxyuridine is discussed in more detail. The cytochemistry required for this analysis is reviewed as are its applications to: (a) determination of the fractions of cells in the G1-, S- and G2 + M phases of the cell cycle; (b) determination of the G1-, S- and G2 + M phase durations and dispersions and growth fraction for asynchronous cells; (c) detection of ara-C resistant cells present at low frequency in an otherwise sensitive population; ...
TY - JOUR. T1 - The Aspergillus nidulans snt genes are required for the regulation of septum formation and cell cycle checkpoints. AU - Kraus, Peter R.. AU - Harris, Steven D.. PY - 2001/11/17. Y1 - 2001/11/17. N2 - In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear division before forming a septum. Previous genetic results suggest that the ability to separate nuclear division and septum formation depends upon a threshold level of activity of the cyclin-dependent kinase NIMX,cdk1. Mutations in nimX and nimT, the gene encoding the NIMXcdk1-activating phosphatase, have revealed that Tyr-15 phosphorylation is important for determining the timing of the formation of the first septum. Here, we describe a screen for suppressors of nimT23 (snt), designed to identify additional components of the pathway regulating septum formation. We show that a subset of the snt mutants are defective in the temporal regulation of septum formation and in cell cycle checkpoint responses. ...
Nitrogen Cycle Process Essay. Essay on the Nitrogen Cycle - Biology Discussion on the nitrogen cycle. Nitrogen is one of In nitrogen cycle, free N2 gas of atmosphere is converted into ammonia or oxidised to nitrate at different stages. Blue green algae In this process nitrogen in organic matter of dead plants and animals is converted to ammonia and amino acids. Urea is applied in nbsp; The Nitrogen Cycle is the Most Important Biogeochemical Cycle about The Process of Nitrogen Cycle - The environment is stabilized by the biogeochemical cycles. Biogeochemical cycles are the processes that occur naturally and recycle the nutrients in different chemical forms from the non-living ecosystem to living organisms and then back to the non-living ecosystem. Free nitrogen cycle Essays and Papers - of Nitrogen Cycle - The environment is stabilized by the biogeochemical cycles. Biogeochemical cycles are the processes that occur naturally and recycle the nutrients in different chemical forms from the ...
TY - JOUR. T1 - Cell-cycle-based strategies to drive myocardial repair. AU - Zhu, Wuqiang. AU - Hassink, Rutger J.. AU - Rubart, Michael. AU - Field, Loren J.. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/7. Y1 - 2009/7. N2 - Cardiomyocytes exhibit robust proliferative activity during development. After birth, cardiomyocyte proliferation is markedly reduced. Consequently, regenerative growth in the postnatal heart via cardiomyocyte proliferation (and, by inference, proliferation of stem-cell-derived cardiomyocytes) is limited and often insufficient to affect repair following injury. Here, we review studies wherein cardiomyocyte cell cycle proliferation was induced via targeted expression of cyclin D2 in postnatal hearts. Cyclin D2 expression resulted in a greater than 500-fold increase in cell cycle activity in transgenic mice as compared to their nontransgenic siblings. Induced cell cycle activity resulted in infarct regression and concomitant improvement in ...
The aim of the present work was to investigate the occurrence of the cell cycle during germination as related to thermodormancy in barley (Hordeum vulgare L., cv. Pewter) grains in relation with abscisic acid (ABA) by: (i) flow cytometry to determine the progression of the cell cycle; and (ii) reverse transcription-PCR to characterize the expression of some important genes involved in cell-cycle regulation. In dry embryos, cells are mostly (82%) arrested in G1 phase of the cell cycle, the remaining cells being in the G2 (17%) or S phase (0.9%). Germination at 20 °C was associated with an increase in the nuclei population in G2 and S (up to 32.5-44.5 and 9.2-11.3%, respectively, after 18-24h). At 30 °C, partial reactivation of the cell cycle occurred in embryos of dormant grains that did not germinate. Incubation with 50mM hydroxyurea suggests that thermodormancy resulted in a blocking of the nuclei in the S phase. In dry dormant grains, transcripts of CDKA1, CYCA3, KRP4, and WEE1 were present, while
Author Summary Cellular and viral life cycles are connected through multiple, though poorly understood, mechanisms. Parvoviruses infect humans and a broad spectrum of animals, causing a variety of diseases, but they are also used in experimental cancer therapy and serve as vectors for gene therapy. Parvoviruses can only multiply in proliferating cells providing essential replicative and transcriptional functions. However, it is unknown whether the cell cycle regulatory machinery may also control parvovirus assembly. We found that the nuclear translocation of parvovirus MVM capsid subunits (VPs) was highly dependent on physiological cell cycle regulations in mammalian fibroblasts, including: quiescence, progression through G1/S boundary, DNA synthesis, and cell to cell contacts. VPs nuclear translocation was significantly more sensitive to cell cycle controls than viral genome replication and gene expression. The results support nuclear capsid assembly as the major driving process of parvoviruses