• 4. Mechanisms of Mitosis I: Spindle assembly. (ucdavis.edu)
  • The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (rupress.org)
  • Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
  • Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
  • Plk1, the most thoroughly characterized member among the mammalian Plks, has multiple important roles in mitosis and cytokinesis, such as centrosome maturation, bipolar spindle formation, kinetochore-microtubule dynamics, activation of the anaphase promoting complex, chromosome segregation and execution of cytokinesis [ 3 , 4 , 13 ]. (oncotarget.com)
  • Inhibition of DNA-PKcs activity via a small interfering RNA or a kinase inhibitor results in mitosis delay, abnormal spindle formation, and chromosome misalignment. (amegroups.org)
  • Inhibition of NEK6 can lead to the termination of mitosis, chromatin spindle defects, and abnormal chromosomal differentiation [ 5 - 7 ]. (hindawi.com)
  • Similar to these drugs, eribulin is a microtubule inhibitor that induces apoptosis of cancer cells by stopping mitosis in the G2/M phase of the cell cycle . (shu.edu)
  • 11. The metaphase-anaphase transition and the spindle checkpoint. (ucdavis.edu)
  • The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
  • Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
  • The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine assay, propidium iodide (PI) staining, annexin V-fluorescein isothiocyanate/PI staining, and transwell assay were employed to test the proliferation, apoptosis, migration ability, and invasiveness of COAD cells. (hindawi.com)
  • Upregulating the level of miR-323a-3p impaired the proliferation, migration, and invasion of COAD cells and promoted apoptosis, whereas supplementing NEK6 alleviated the damage of the proliferation, migration, and invasion of COAD cells caused by miR-323a-3p and inhibited miR-323a-3p-induced apoptosis. (hindawi.com)
  • These findings indicate that miR-323a-3p regulates the proliferation, migration, invasion, and apoptosis of COAD cells by targeting NEK6. (hindawi.com)
  • To attempt to identify the relationship of the key regulator molecules in paclitaxel-induced apoptosis using two metastatic cell lines: the human prostate carcinoma LNCaP line and the cervical carcinoma HeLa cell line. (johnshopkins.edu)
  • Analysis of synchronized HeLa cells demonstrated that endogenous bcl-2 is phosphorylated in a G 2 /M cell cycle- dependent manner without apoptosis. (johnshopkins.edu)
  • In addition, we confirmed that the death-decision of paclitaxel-induced apoptosis is not mediated by bcl-2 phosphorylation and believe that this decision may be mediated by the activated spindle assembly checkpoint. (johnshopkins.edu)
  • The novel PLK1 inhibitor, onvansertib, is the first available for oral administration and has shown tumor growth inhibition in hematologic tumors, osteosarcoma, ovarian carcinoma, breast cancer and colon adenocarcinoma cells. (childrenscolorado.org)
  • Here we identify two critical motifs within BubR1M that contribute to Cdc20 binding and anaphase-promoting complex/cyclosome inhibition: a destruction box (D box) and a phenylalanine-containing motif termed the Phe box.ABubR1 mutant lacking these motifs is defective in MCC maintenance in mitotic human cells but is capable of supporting spindle-checkpoint function. (elsevierpure.com)
  • Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
  • DNA-PKcs activation, as monitored by DNA-PKcs phosphorylation, is physically and functionally associated with mitotic spindle formation. (amegroups.org)
  • Both LNCaP and HeLa cells were continuously exposed to clinically achievable concentrations of paclitaxel and observed for activation of programmed cell death as measured by cytotoxic dose-response curves, poly(adenosine diphosphate-ribose) polymerase cleavage, bcl-2 phosphorylation, and the activation of caspase-7 (interleukin-1 beta converting enzyme (ICE)-LAP3). (johnshopkins.edu)
  • Initially, we asked whether paclitaxel-induced bcl-2 phosphorylation is triggered by the spindle assembly checkpoint via an active cdc2 kinase-dependent pathway and whether phosphorylation of endogenous bcl-2 is the signal that activates cell death machinery. (johnshopkins.edu)
  • Paclitaxel-induced G 2 /M cell cycle arrest correlated with cdc2 kinase activity and bcl-2 phosphorylation. (johnshopkins.edu)
  • These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
  • Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. (shu.edu)
  • For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
  • The oncogenic kinase PLK1 controls cell cycle and growth and is a cancer therapeutic target. (childrenscolorado.org)
  • Polo-like kinase-1 (PLK1) is highly expressed in rapidly dividing normal cells and is overexpressed in many types of cancer, including Group 3 medulloblastoma, and is associated with poor prognosis. (childrenscolorado.org)
  • p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
  • In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
  • A key issue is how cells pair sister chromatids but preclude the catastrophic pairing of nonsister chromatids. (rupress.org)
  • Enduring and robust, structural cohesins resist poleward-pulling forces produced by the mitotic spindle that act to separate sister chromatids and must often persist for extended periods of time in meiosis. (rupress.org)
  • The centrosome cycle (1 or 2 MTOC indicates microtubule organizing centers) is shown to be coordinated with the DNA/chromosome cycle (2N or 4N DNA content). (shu.edu)
  • MCC is a critical checkpoint inhibitor of the anaphase-promoting complex/ cyclosome, a ubiquitin ligase required for anaphase onset. (elsevierpure.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
  • Genes that suppress carcinogenesis have been classified as gatekeepers that regulate cellular proliferation and cell death and as caretakers that are primarily encode DNA repair proteins required for the maintenance of genome integrity ( 15 ). (amegroups.org)
  • It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
  • Furthermore, DNA-PKcs is required to prevent mitotic catastrophe in response to DNA damage ( 13 ). (amegroups.org)
  • The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. (nature.com)
  • Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC. (nature.com)
  • Musacchio, A. The molecular biology of spindle assembly checkpoint signaling dynamics. (nature.com)
  • Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
  • In your first year, your modules give you an insight into various biological and chemical disciplines, including biochemistry, cell and molecular biology, microbiology and physiology. (kent.ac.uk)
  • Your second year builds on this knowledge and covers areas such as gene regulation, cell biology and metabolism. (kent.ac.uk)
  • Its apparent dispensability in the spindle checkpoint might be due to functional duality or redundant, competing mechanisms. (elsevierpure.com)
  • Our results indicate that the events associated with paclitaxel-induced cytotoxicity are connected to each other and represent the signaling network of paclitaxel-induced mitotic arrest and cell death. (johnshopkins.edu)
  • This illustration shows the proposed relative location of the 2 known cell cycle arrest points in cells with MTD (microtubule damage). (shu.edu)
  • Unattached or tensionless kinetochores activate the checkpoint and enhance the production of the mitotic checkpoint complex (MCC) consisting of BubR1, Bub3, Mad2, and Cdc20. (elsevierpure.com)
  • Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
  • Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
  • Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
  • 23. S-phase entry in Mammals and Checkpoints. (ucdavis.edu)
  • Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)
  • G1MTC, G1 phase microtubule checkpoint. (shu.edu)
  • The arrests the cell cycle in G1 phase between the shift from a low cdc2-expressing state to a high cdc2-expressing state. (shu.edu)
  • miRNAs expressed in a wide variety of human cancers can regulate posttranscriptional gene expression by binding to the 3′ untranslated region of the target mRNAs and act as oncogenes or tumor suppressors to regulate cell signaling pathways, affecting tumorigenesis and tumor progression [ 17 ]. (hindawi.com)
  • These studies unveiled a novel function of DNA-PKcs in safeguarding the genome integrity and cancer suppression as chromosomal instability (CIN) plays an important role in cancer development and is a hallmark of cancer cells ( 14 ). (amegroups.org)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • DNA-PKcs and the NHEJ pathway are also essential for V(D)J recombination during T and B cell lymphocyte development. (amegroups.org)
  • The activity of NEK6 is enhanced in several cancer cells, including colon adenocarcinoma (COAD) cells. (hindawi.com)
  • An investigation of PLK1 expression in DepMap found PLK1 is a critical mediator in 55 central nervous system cell lines, including eight medulloblastoma cell lines. (childrenscolorado.org)
  • In COAD cells, NEK6 was highly expressed, whereas miR-323a-3p was expressed at low levels and negatively regulated NEK6. (hindawi.com)