M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.G2 Phase Cell Cycle Checkpoints: CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.S Phase Cell Cycle Checkpoints: Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.G1 Phase Cell Cycle Checkpoints: Regulatory signaling systems that control the progression of the CELL CYCLE through the G1 PHASE and allow transition to S PHASE when the cells are ready to undergo DNA REPLICATION. DNA DAMAGE, or the deficiencies in specific cellular components or nutrients may cause the cells to halt before progressing through G1 phase.Allyl CompoundsCell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.Isothiocyanates: Organic compounds with the general formula R-NCS.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Checkpoint Kinase 2: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.Cell Line, Tumor: A cell line derived from cultured tumor cells.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Genes, cdc: Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Ataxia Telangiectasia Mutated Proteins: A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.DNA Replication: The process by which a DNA molecule is duplicated.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.Ataxia Telangiectasia: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).Radiation, Ionizing: ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.G0 Phase: A quiescent state of cells during G1 PHASE.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Schizosaccharomyces pombe Proteins: Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mimosine: 3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Interphase: The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).Fungal Proteins: Proteins found in any species of fungus.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).BRCA1 Protein: The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Centrosome: The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Blastula: An early non-mammalian embryo that follows the MORULA stage. A blastula resembles a hollow ball with the layer of cells surrounding a fluid-filled cavity (blastocele). The layer of cells is called BLASTODERM.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.14-3-3 Proteins: A large family of signal-transducing adaptor proteins present in wide variety of eukaryotes. They are PHOSPHOSERINE and PHOSPHOTHREONINE binding proteins involved in important cellular processes including SIGNAL TRANSDUCTION; CELL CYCLE control; APOPTOSIS; and cellular stress responses. 14-3-3 proteins function by interacting with other signal-transducing proteins and effecting changes in their enzymatic activity and subcellular localization. The name 14-3-3 derives from numerical designations used in the original fractionation patterns of the proteins.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Exonucleases: Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Genes, Fungal: The functional hereditary units of FUNGI.1-Naphthylamine: A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Menstrual Cycle: The period from onset of one menstrual bleeding (MENSTRUATION) to the next in an ovulating woman or female primate. The menstrual cycle is regulated by endocrine interactions of the HYPOTHALAMUS; the PITUITARY GLAND; the ovaries; and the genital tract. The menstrual cycle is divided by OVULATION into two phases. Based on the endocrine status of the OVARY, there is a FOLLICULAR PHASE and a LUTEAL PHASE. Based on the response in the ENDOMETRIUM, the menstrual cycle is divided into a proliferative and a secretory phase.X-Rays: Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Cyclin-Dependent Kinase Inhibitor p16: A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.Kinetics: The rate dynamics in chemical or physical systems.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Exodeoxyribonucleases: A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Infrared Rays: That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Ploidies: The degree of replication of the chromosome set in the karyotype.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.DNA, Neoplasm: DNA present in neoplastic tissue.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Colonic Neoplasms: Tumors or cancer of the COLON.Proto-Oncogene Proteins c-mdm2: An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.Breast Neoplasms: Tumors or cancer of the human BREAST.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.DNA Helicases: Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-.Proto-Oncogene Proteins c-myc: Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.PhosphoproteinsAdaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesCDC28 Protein Kinase, S cerevisiae: A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Recombinant Proteins: Proteins prepared by recombinant DNA technology.

*  AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells | Journal of Cell Science

In the cell cycle, Ca2+ regulates progression through several checkpoints, including the G1-S-phase transition, G2-M-phase ... Westerlund, U., Moe, M. C., Varghese, M., Berg-Johnsen, J., Ohlsson, M., Langmoen, I. A. and Svensson, M. (2003). Stem cells ... 2A). However, the proportion of cells in G2-M phase was increased in Aqp4-/- ANSCs (6.7±0.3%) compared with the Aqp4+/+ cells ( ... The proportion of G2-M phase cells was increased in Aqp4-/- ANSCs compared with the wild type (*P,0.05, n=3). Moreover, AQP4 ...

*  Module 2: Cells, Microscopes, Biological Molecules, Nucleotides, Enzymes, Membranes, Cell Division. - Revision Cards in A Level...

The cell cycle is regulated by checkpoints. These occur at key points of the process to make sure it is okay for the cycle to ... M phase- mitosis and cytokinesis.. *Interphase is subdivided into three seperate growth stages. These are called G1, S and G2. ... Synthesis- cell replicates its DNA ready to divide by mitosis.. *G2- cell keeps growing and proteins needed for cell division ... In animals, adult cells are used to replace damaged cells.. *Plants are always growing, so stem cells are needed to make new ...

*  ANAPC16 Gene - GeneCards | APC16 Protein | APC16 Antibody

APC-Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint ... a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The ... The GeneCards human gene database index: 2 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z ... a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The ...

*  JCI - The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid...

Hixon, M.L., Gualberto, A. 2003. Vascular smooth muscle polyploidization - from mitotic checkpoints to hypertension. Cell Cycle ... hepatocytes enter the cell cycle. Mitogenic treatment with EGF allowed these cells to progress synchronously into S phase at 48 ... Wu, M.Y., Cully, M., Andersen, D., Leevers, S.J. 2007. Insulin delays the progression of Drosophila cells through G2/M by ... Ravid, K., Lu, J., Zimmet, J.M., Jones, M.R. 2002. Roads to polyploidy: the megakaryocyte example. J. Cell. Physiol. 190:7-20. ...

*  Loss of PHLPP expression in colon cancer: Role in proliferation and tumorigenesis

... in an increase in the percentage of cells in the G2 phase suggesting a potential block of the G2/M transition in the cell cycle ... isoforms inhibit cell proliferation primarily by interfering with the different cell cycle checkpoints in colon cancer cells. ... To further determine whether PHLPP inhibits cell proliferation by interfering with the cell cycle, we examined the cell cycle ... Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle. 2003;2:339-45. [PubMed] ...

*  Professor Catherine Green - Nuffield Department of Medicine

... and in cells arrested in S or G2/M phases while a single form was observed in G1-arrested cells. Treatment with various DNA ... demonstrating cell-cycle stage specificity of the checkpoint genes in this response to DNA damage. Analysis of checkpoint ... whereas in rad9Delta-rad24Delta cells the G1/S checkpoint is undetectable, although there is a residual G2/M checkpoint. We ... cell-cycle arrest and transcriptional induction) and was cell-cycle stage- and progression-independent. In asynchronous ...

*  CDC25A

M-phase inducer phosphatase 1; cell division cycle 25 homolog A (S. cerevisiae); cell division cycle 25 homolog A (S. pombe); ... Checkpoint Assays * Signaling Pathways Cell division cycle 25 homolog A (CDC25A). Target Class. Pathway. Family. Cell Cycle ... CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by ... Cell Cycle Protein ? DiscoveRx offers cell-based assays that target other members of this gene family or functional group. ...

*  Plus it

... colon carcinoma cells. This is of high importance as the cell cycle response to 5-FU treatment in colorectal carcinoma cells ... Ad-WT lysed both normal and tumor cells. Cells were photographed under phase-contrast light microscope 7 d after the initiation ... Dabrowska A, Szary J, Kowalczuk M, Szala S, Ugorski M. CEA-negative glioblastoma and melanoma cells are sensitive to cytosine ... it showed intratumor replicating capacity similar to that attained in breast cancer for a CRAd that targets the G1-S checkpoint ...

*  Levels of the origin-binding protein Double parked and its inhibitor Geminin increase in response to replication stress |...

... has a dual role in S-phase progression and at a cell cycle checkpoint. Proc. Natl. Acad. Sci. USA 92, 11791-11795. ... 1C,E). This labeling in G2 and M phase was not observed in the primary stem-cell daughter [ganglion mother cell (GMC)] or cells ... stem cells and lamina-precursor cells in the brain have a low but detectable level of Dup during G2 and M phase. Stem cells ... During a normal cell cycle, Dup is rapidly degraded as cells enter S phase, but the mechanism that coordinates this ubiquitin- ...

*  Phosphorylation of Spc110p by Cdc28p-Clb5p kinase contributes to correct spindle morphogenesis in S. cerevisiae | Journal of...

... contributed to bulk levels and cell-cycle-dependent phosphorylation of Spc110p starting in early S phase, even in the absence ... Huisman, S. M., Bales, O. A., Bertrand, M., Smeets, M. F., Reed, S. I. and Segal, M. (2004). Differential contribution of Bud6p ... and monitored by checkpoint pathways to accurately coordinate chromosomal segregation with other events in the cell cycle. We ... Contribution of Mps1p to cell-cycle-dependent phosphorylation of Spc110p. (A) Cell-cycle-dependent phosphorylation of Spc110p ...

*  CDC25A (phospho T507) polyclonal antibody - (PAB0430) - Products - Abnova

M-phase inducer phosphatase 1,cell division cycle 25A,dual specificity phosphatase CDC25A ... Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint.. ... CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by ... Goloudina A, Yamaguchi H, Chervyakova DB, Appella E, Fornace AJ Jr, Bulavin DV.Cell Cycle. 2003 Sep-Oct;2(5):473-8. ...

*  Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila |...

G2/M and M/G1 cell-cycle transitions. Development 131,3169 -3181. ... controlled by Cyclin E and lacks a checkpoint ensuring S-phase ... Akt then controls cell survival, cell cycle, cell growth and metabolism through phosphorylation of a number of key substrates, ... Lilly, M. A. and Duronio, R. J. (2005). New insights into cell cycle control from the Drosophila endocycle. Oncogene 24,2765 - ... Puig, O., Marr, M. T., Ruhf, M. L. and Tjian, R. (2003). Control of cell number by Drosophila FOXO: downstream and feedback ...

*  Opdivo (nivolumab) Stabilized Patient-reported Outcomes in Patients With Previously Treated Recurrent or Metastatic Squamous...

Stabilized Patient-Reported Outcomes in Patients With Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the ... Cell Carcinoma of the Head and Neck in Pivotal Phase 3 CheckMate -141 Study Opdivo-treated patients exhibited stable ... In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. ... John O'Donnell, Ph.D., M.A., vice president, head, Health Economics and Outcomes Research, Bristol-Myers Squibb, commented, "At ...

*  Plus it

... indicate that cell death was not restricted to one particular phase of the cell cycle and confirm the ability of flavopiridol ... suggesting flavopiridol-mediated arrest of cell cycle progression at the G2 checkpoint. Although no significant change in the G ... 3B⇓ . The 1-kb ladder is shown (M). D, assessment of CytC cytosolic content. LAN-5 cells were treated for the indicated time ... Rollins BJ Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin ...

*  Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis |...

Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition. Nat. Cell Biol. 4, 111-116. ... preventing premature initiation of mitotic events during S phase or when the DNA damage checkpoint is induced, to allow time ... Field, C. M. and Alberts, B. M. (1995). Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J ... 4G,G′) are shown, along with corresponding 16 cell and 64 cell controls (Fig. 4C,E). Moreover, in both 64-cell and 128-cell ...

*  Plus it

During cell cycle progression, RAD51AP1 started to accumulate in an early S phase and kept high levels of expression to G2-M ... Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 2003;193:91 ... Cell lines and tissue specimens. TFK-1 and HuH28 (two human ICC cell lines) were obtained from Cell Resource Center for ... Next, we evaluated its detailed subcellular localization during cell cycle progression by synchronizing ETK-1 cells with ...

*  Plus it

Lobrich M. . Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair ( ... S3; Table 1). Compared with exponentially growing HT29 cells, the plateau phase HT29 cells were enriched in the G1 cell cycle ... The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005;7:195-201. ... Abrogation of cell cycle checkpoints was evaluated by flow cytometry. Exponentially growing cells were exposed to a single dose ...

*  Plus it

E6 and E7 interfere with normal cell cycle checkpoint processes and induce cell division. ... Muderspach L., Wilczynski S., Roman L., Bade L., Felix J., Small L. A., Kast W. M., Fascio G., Marty V., Weber J. A Phase I ... Palefsky J. M., Holly E. A., Hogeboom C. J., Ralston M. L., DaCosta M. M., Botts R., Berry J. M., Jay N., Darragh T. M. ... Ressing M. E., Sette A., Brandt R. M., Ruppert J., Wentworth P. A., Hartman M., Oseroff C., Grey H. M., Melief C. J., Kast W. M ...

*  Slk19-dependent mid-anaphase pause in kinesin-5-mutated cells | Journal of Cell Science

Cells were arrested in S-phase of the cell cycle for 2 hours and then released from arrest. The distance between spindle pole ... Pinsky, B. A., Kung, C., Shokat, K. M. and Biggins, S. (2006). The Ipl1-Aurora protein kinase activates the spindle checkpoint ... fast phase, pause phase and slow phase) are indicated at the bottom of the frames. (A) kip1Δ cells; (B) kip1Δ cin8-FA cells. ... Cells expressing Scc1-HA were arrested in S-phase of the cell cycle by hydroxyurea then processed for tubulin immunostaining ...

*  Plus it

Disjointed cell cycle phase-related activity accounts for synergistic outcome in metastatic non-small cell lung cancer cells ( ... 20 mm Tricine, 1.5 mm MgSO4 (anhydrous), 0.1 mm EDTA, 33 mm DTT, 0.2 mg/ml acetyl-CoA, 0.5 mm ATP, and 6.0 mm MgCO3] to each ... Cells were growth arrested at the G1-S checkpoint similar to TGF-β. Consistent with the G1-S arrest, A-161906 induced the ... 10 mm Tris-HCl (pH 7.4), 10 mm EDTA, 1 mm DTT, 100 mm urea, and protease inhibitors]. Samples were centrifuged at 13,000 × g ...

*  Plus it

C.-M. Tang reports receiving commercial research grants from Bria Cell and holds ownership interest (including patents) in ... ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control. J Biol Chem 2011;286:31542- ... Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. ... PD-L1/PD-1 immune blockade drugs (e.g., nivolumab and pembrolizumab) are potent immune checkpoint inhibitors that have been ...

*  Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21...

Reichert M, Saur D, Hamacher R, Schmid RM, Schneider G. Phosphoinositide-3-kinase signaling controls S-phase kinase-associated ... HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from ... h of incubation, simvastatin arrested cell cycle progression at the G0/G1 phase in HepG2 cells in a dose-dependent manner. The ... Simvastatin-induced p27 upregulation was Skp2-dependent and promoted G0/G1 phase cell cycle arrest in HepG2 cells. (a) ...

*  CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly | Journal of Cell Science

Dunleavy, E. M., *Almouzni, G. and *Karpen, G. H.. (2011). H3.3 is deposited at centromeres in S phase as a placeholder for ... 2009). HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell 137, 485-497. doi: ... 5B), which are thought to be involved in regulating kinetochore activity through the spindle assembly checkpoint, did not ... Cheeseman, I. M.. (2014). Polo-like kinase 1 licenses CENP-A deposition at centromeres. Cell 158, 397-411. doi:10.1016/j.cell. ...

*  Protein kinase elisa and antibody

Abundant expression accelerates the exit when cells are in M-phase and also delays the entry into mitosis when cells are in G2 ... is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote ... Serine/threonine kinase which activates checkpoint signaling upon genotoxic stresses. Involved in G2 arrest following DNA ... In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation ...

*  Reciprocal regulation of signaling and endocytosis: Implications for the evolving cancer cell | JCB

M.S. Robinson. . 2006. Functional analysis of AP-2 alpha and mu2 subunits. Mol. Biol. Cell. 17:5298-5308. doi:10.1091/mbc.E06- ... Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint. Dev. Cell ... Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. Science. 233:1061-1068. ... Cell Cycle. 11:3611-3626. doi:10.4161/cc.21920. OpenUrlCrossRefPubMed ...

Sunda (asura): A mythological character from the great epic Mahabharata, Sunda (सुन्‍द) was an asura prince and the brother of Upasunda. Their father was Jambha.Start point (yeast): The Start checkpoint is a major cell cycle checkpoint in yeast. The Start checkpoint ensures irreversible cell-cycle entry even if conditions later become unfavorable.Organosulfur compounds: Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.Allyl isothiocyanateBookmarking: Bookmarking (also "gene bookmarking" or "mitotic bookmarking") refers to a potential mechanism of transmission of gene expression programs through cell division.G2-M DNA damage checkpoint: The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms ranging from yeast to mammals. This checkpoint ensures that cells don't initiate mitosis before they have a chance to repair damaged DNA after replication.Serine/threonine-specific protein kinaseMinC: The MinC protein is one of three proteins encoded by the minB operon and which is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. This function is achieved by preventing the formation of the divisome Z-ring around the poles.P53: Tumor protein p53, also known as p53, cellular tumor antigen p53 (UniProt name), phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). This homolog (originally thought to be, and often spoken of as, a single protein) is crucial in multicellular organisms, where it prevents cancer formation, thus, functions as a tumor suppressor.Hyperphosphorylation: Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signalling mechanisms used by the cell to regulate mitosis.Kinome: In molecular biology, the kinome of an organism is the set of protein kinases in its genome. Kinases are enzymes that catalyze phosphorylation reactions (of amino acids) and fall into several groups and families, e.Base excision repair: frame|right|Basic steps of base excision repair|Basic steps of base excision repairCyclin: Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes.DNA-binding proteinFlow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.DNA re-replication: DNA re-replication (or simply rereplication) is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers.Clb 5,6 (Cdk1): Clb5 and Clb6 are B-type, S-phase cyclins in yeast that assist in cell cycle regulation.Morgan, DO (2007) 'The Cell Cycle: Principles of Control, Oxford University Press Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase.Gamma counter: A gamma counter is a machine to measure gamma radiation emitted by a radionuclide. A large number of samples are placed in sealed vials or test tubes, and move along a serpentine track on a horizontal plane.Hydroxyurea dermopathyAtaxia telangiectasia mutated: Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis.Spindle apparatus: In cell biology, the spindle apparatus refers to the subcellular structure of eukaryotic cells that separates chromosomes between daughter cells during cell division. It is also referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.Pocket protein family: Pocket protein family consists of three proteins:Cyclin-dependent kinase complex: A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic subunit of a protein kinase, cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin.Malumbres M, Barbacid M.Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.NocodazoleCyclin D/Cdk4: The Cyclin D/Cdk4 complex is a multi-protein structure consisting of the proteins Cyclin D and cyclin-dependent kinase 4, or Cdk4, a serine-threonine kinase. This complex is one of many cyclin/cyclin-dependent kinase complexes that are the "hearts of the cell-cycle control system" and govern the cell cycle and its progression.UVB-induced apoptosis: UVB-induced apoptosis is the programmed cell death of cells that become damaged by ultraviolet rays. This is notable in skin cells, to prevent melanoma.Zuotin: Z-DNA binding protein 1, also known as Zuotin, is a Saccharomyces cerevisiae yeast gene.Schizosaccharomyces pombe: Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped.Dermal fibroblast: Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers.Histone octamer: A histone octamer is the eight protein complex found at the center of a nucleosome core particle. It consists of two copies of each of the four core histone proteins (H2A, H2B, H3 and H4).Coles PhillipsMimosineMatrix model: == Mathematics and physics ==Antileukemic drug: Antileukemic drugs, anticancer drugs that are used to treat one or more types of leukemia, include:DNA condensation: DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems.Kinetochore: The kinetochore is the protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.Pituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.Proximity ligation assay: Proximity ligation assay (in situ PLA) is a technology that extends the capabilities of traditional immunoassays to include direct detection of proteins, protein interactions and modifications with high specificity and sensitivity. Protein targets can be readily detected and localized with single molecule resolution and objectively quantified in unmodified cells and tissues.Hippo signaling pathway: The Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway, controls organ size in animals through the regulation of cell proliferation and apoptosis. The pathway takes its name from one of its key signaling components—the protein kinase Hippo (Hpo).Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingAdaptive response: The adaptive response is a form of direct DNA repair in E. coli that protects DNA from damage by external agents or by errors during replication.Metaphase: Metaphase (from the Greek μετά, "adjacent" and φάσις, "stage") is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase. These chromosomes, carrying genetic information, align in the equator of the cell before being separated into each of the two daughter cells.Concentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.Bivalent chromatin: Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes.Centrosome cycle: Centrosomes are the major microtubule organizing center (MTOC) in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy.Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.

(1/221) Spindle assembly checkpoint-related failure perturbs early embryonic divisions and reduces reproductive performance of LT/Sv mice.

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(2/221) The nucleoporin Nup153 affects spindle checkpoint activity due to an association with Mad1.

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(3/221) Unliganded progesterone receptors attenuate taxane-induced breast cancer cell death by modulating the spindle assembly checkpoint.

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(4/221) RNA binding protein CUGBP2/CELF2 mediates curcumin-induced mitotic catastrophe of pancreatic cancer cells.

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(5/221) Aneuploidy and tumorigenesis.

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(6/221) Correction of microtubule-kinetochore attachment errors: mechanisms and role in tumor suppression.

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(7/221) Mutual regulation between the spindle checkpoint and APC/C.

 (+info)

(8/221) Polycomb protein EZH2 regulates cancer cell fate decision in response to DNA damage.

 (+info)



kinase

  • Stable overexpression of either PHLPP isoform in colon cancer cells decreased the rate of cell proliferation and sensitized the cells to growth inhibition induced by the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002, whereas knockdown of either PHLPP isoform by shRNA promoted the proliferation of DLD1 cells. (pubmedcentralcanada.ca)
  • Loss of Clb5p-dependent kinase abolishes intrinsic asymmetry between the spindle poles resulting in lethal translocation of the spindle into the bud with high penetrance in diploid cells. (biologists.org)
  • We found that Clb5p-GFP was localised to the spindle poles and intranuclear microtubules and that Clb5p-dependent kinase promoted cell cycle dependent phosphorylation of Spc110p contributing to spindle integrity. (biologists.org)
  • Activation of the Raf-1/MEK/Erk kinase pathway by a novel Cdc25 inhibitor in human prostate cancer cells. (abnova.com)
  • A conserved molecular mechanism that controls entry into mitosis in eukaryotic cells involves the activation of a cyclin-dependent kinase called Cdk1, which serves as a master regulator of early mitotic events ( O'Farrell, 2001 ). (biologists.org)
  • Inhibition of checkpoint kinase 1 has been shown to enhance the cytotoxicity of DNA-damaging targeted chemotherapy through cell cycle checkpoint abrogation and impaired DNA damage repair. (aacrjournals.org)
  • A novel checkpoint kinase 1/2 inhibitor, AZD7762, was evaluated for potential enhancement of radiosensitivity for human tumor cells in vitro and in vivo xenografts. (aacrjournals.org)
  • This study reports the evaluation of a novel checkpoint kinase inhibitor (AZD7762) as a radiation sensitizer. (aacrjournals.org)
  • Critical downstream molecules in these pathways are the checkpoint kinase (Chk)1 and Chk2 threonine kinases, which facilitate both the G 1 and G 2 checkpoints. (aacrjournals.org)

progression

  • Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. (genecards.org)
  • CDC25A is required for progression from G1 to the S phase of the cell cycle. (discoverx.com)
  • Cell-cycle progression in all eukaryotes is coupled to the oscillatory activation of cyclin-dependent kinases (CDKs). (biologists.org)
  • Mechanistically, InR/Foxo signaling controls cell cycle progression by modulating dmyc expression and dMyc transcriptional activity. (biologists.org)
  • CheckMate -141 is a Phase 3, open-label, randomized trial that evaluated Opdivo versus investigator's choice of therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with tumor progression within six months of platinum therapy in the adjuvant, primary, recurrent or metastatic setting. (businesswire.com)
  • Based on these observations, we propose that Myt1 serves unique Cdk1 regulatory functions required for efficient coupling of cell differentiation with cell cycle progression. (biologists.org)
  • Notably, suppression of RAD51AP1 by short interfering RNA resulted in growth suppression of cholangiocarcinoma cells, suggesting its involvement in the development and/or progression of ICC. (aacrjournals.org)
  • Blocks that occur in G 1 and G 2 following treatment with radiation and DNA-damaging drugs have been called checkpoints and are presumed to allow DNA damage repair before further cell cycle progression ( 1 ). (aacrjournals.org)
  • Inhibition of these kinases (particularly Chk1) can result in the abrogation of cell cycle progression, premature entry into the cell cycle following DNA damage, and insufficient DNA repair ( 8 ). (aacrjournals.org)

kinases

  • We find that a range of defects in DNA replication stabilize Dup protein and that this stabilization is not dependent on ATM/ATR checkpoint kinases. (biologists.org)
  • Spindle morphogenesis is regulated by cyclin-dependent kinases and monitored by checkpoint pathways to accurately coordinate chromosomal segregation with other events in the cell cycle. (biologists.org)
  • These differences in Wee1 and Myt1 protein localization and target site specificity suggest that the metazoan Cdk1 inhibitory kinases have evolved distinct cell cycle regulatory functions required at different stages of development. (biologists.org)
  • AZD7762 inhibits downstream checkpoint kinases 1 and 2 of the ATM/ATR DNA damage response pathway. (aacrjournals.org)
  • One consequence of this signaling is that cells are arrested in the G 1 phase of the cell cycle due, in part, to the induction of several specific inhibitors of the cyclin-dependent kinases p15 and p21 ( 1 ). (aacrjournals.org)

inhibition

  • In addition, we demonstrated that the PHLPP-mediated growth inhibition in colon cancer cells was largely rescued by overexpression of a constitutively active Akt. (pubmedcentralcanada.ca)
  • Through several CDK targets and Gem inhibition, it appears that the cell has taken a multipronged approach to preventing the catastrophic mistake of unbalanced genomic replication. (biologists.org)
  • Cell death was preceded by DNA synthesis inhibition and G 1 -G 2 arrest, reversed by the pancaspase inhibitor, zVAD-fmk, and associated with caspase-3 and -2 activation and CytC increase. (aacrjournals.org)
  • TGF-β produces profound growth inhibition on many types of cells, including normal epithelia, induces a differentiated phenotype, and has the potential to produce an apoptotic response in various cell types ( 1 - 3 ). (aacrjournals.org)
  • Another component of the TGF-β response is the alteration of cell phenotype by induction of cellular differentiation that results in growth inhibition and terminal differentiation to a mature phenotype ( 6 ). (aacrjournals.org)

proliferation

  • Serving as a major regulator downstream of PI3K, Akt promotes tumor growth by promoting cell proliferation and inhibiting apoptosis ( Manning & Cantley, 2007 ). (pubmedcentralcanada.ca)
  • Cdc25A and cdc25B expression in malignant lymphoma of the thyroid: correlation with histological subtypes and cell proliferation. (abnova.com)
  • Similar to InR/Tor signaling, Myc has an evolutionarily conserved function in promoting cell growth and proliferation ( de la Cova and Johnston, 2006 ). (biologists.org)
  • This regulatory mechanism, which prevents Cdk1 from triggering premature mitotic events, is also induced during the DNA damage response and used to coordinate cell proliferation with crucial developmental events. (biologists.org)
  • These data suggest that RAD51AP1 may play a role in cell proliferation as well as DNA repair. (aacrjournals.org)
  • In this paper, we reveal that RAD51 associating protein-1 (RAD51AP1) is commonly overexpressed in ICCs and that its expression is associated with proliferation of cancer cells. (aacrjournals.org)
  • A-161906 inhibited the proliferation of multiple cell lines in a concentration-dependent manner. (aacrjournals.org)

Pathways

  • Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Cell Cycle, Mitotic . (genecards.org)
  • There has been considerable interest in targeting molecular pathways involved with these checkpoints to inhibit repair, particularly in cancer cells ( 2 , 3 ). (aacrjournals.org)

phosphorylation

  • Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. (abnova.com)
  • Akt then controls cell survival, cell cycle, cell growth and metabolism through phosphorylation of a number of key substrates, including the Tsc1-Tsc2 complex, and the transcription factors of the Forkhead box O (FoxO) family. (biologists.org)
  • Once mitotic cyclins are re-synthesized during interphase, Cdk1 is maintained in an inactivate state by inhibitory phosphorylation, preventing premature initiation of mitotic events during S phase or when the DNA damage checkpoint is induced, to allow time for DNA repair. (biologists.org)

pathway

  • Aquaporins are a family of water channel proteins that provide a major pathway for osmotically driven water transport through cell membranes. (biologists.org)
  • The Insulin receptor/Target of rapamycin (InR/Tor) pathway regulates cell size and number and hence organ and body growth across evolution ( Hafen and Stocker, 2003 ). (biologists.org)
  • Both the G 1 and G 2 checkpoints are controlled by the ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and Rad3 related (ATR) signaling pathway ( 2 ). (aacrjournals.org)
  • We also examined the effects of components of the FEAR pathway, which is involved in the early-anaphase activation of Cdc14 regulatory phosphatase, on anaphase spindle elongation in kip1 Δ cin8-F467A cells. (biologists.org)

overexpression

  • Finally, overriding of the pre-anaphase checkpoint by overexpression of Cdc20 also eliminated the mid-anaphase pause and caused DNA deformation during anaphase in kip1 Δ cin8 - F467A cells. (biologists.org)

Saccharomyces

  • We examined spindle elongation in anaphase in Saccharomyces cerevisiae cells mutated for the kinesin-5 motor proteins Cin8 and Kip1. (biologists.org)

induce

  • Collectively, E6 and E7 interfere with normal cell cycle checkpoint processes and induce cell division. (aacrjournals.org)

chromosomal

  • CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. (discoverx.com)

processes

  • We study the processes that occur at replications forks and in replication factories in mammalian cells. (ox.ac.uk)
  • Spindle assembly and polarity establishment are tightly coupled processes in the yeast cell cycle. (biologists.org)

cerevisiae

  • In S. cerevisiae cells, anaphase-B spindle elongation proceeds in two phases. (biologists.org)

eukaryotic cells

vitro

  • AV22EL induced specific in vitro lysis of human CRC cell lines that expressed A33 and have negligible lytic capacity on cells that lacked or had minimal A33 expression, including normal human colonic cells. (aacrjournals.org)
  • AV22EL induced specifically the in vitro lysis of cells of CRC origin while showing almost no lytic activity on other cancer cell lines. (aacrjournals.org)
  • The current study shows that AZD7762 is also a potent radiation sensitizer of p53-compromised cells both in vitro and in vivo . (aacrjournals.org)
  • Cells were deleted for KIP1 and/or expressed one of two motor-domain Cin8 mutants (Cin8-F467A or Cin8-R196K, which differ in their ability to bind microtubules in vitro, with Cin8-F467A having the weakest ability). (biologists.org)

spindle morphogenesis

  • Anaphase-B spindle elongation is the final phase of bipolar spindle morphogenesis, during which the spindle elongates dramatically, as much as two to five times its pre-anaphase length, thus spatially separating sister chromatids. (biologists.org)

novel

  • To address this issue, we have undertaken a functional analysis of Drosophila Myt1 that has revealed novel developmental roles for this conserved cell cycle regulator during gametogenesis. (biologists.org)
  • Recently, a novel Chk inhibitor [3-(carbamoylamino)-5-(3-fluorophenyl)- N -[(3S)-3-piperidyl]thiophene-2 carboxamide, AZDwas shown to enhance the cytotoxicity of DNA-damaging chemotherapy agents by abrogation of the cell cycle arrest ( 9 ). (aacrjournals.org)

Moreover

  • Moreover, re-expression of either PHLPP isoform in HCT116 cells inhibited tumor growth in vivo . (pubmedcentralcanada.ca)
  • Moreover, mitotic index measurements suggested that germline stem cells proliferate more rapidly, in myt1 mutant females. (biologists.org)

protein

  • Cells have to coordinate a large number of activities at each replication fork, and this seems to involve the key replication protein PCNA that acts as a sliding clamp to recruit enzymes and regulators of DNA replication to the right place at the right time. (ox.ac.uk)
  • This project uses fluorescence resonance energy transfer (FRET) to monitor protein-protein interactions in real time in living cells. (ox.ac.uk)
  • This response to replication stress was cell-type specific, with neuroblast stem cells of the larval brain having the largest increase in Dup protein. (biologists.org)
  • Defects at different steps in replication also increased Dup protein during an S-phase-like amplification cell cycle in the ovary, suggesting that Dup stabilization is sensitive to DNA replication and not an indirect consequence of a cell-cycle arrest. (biologists.org)
  • Finally, we find that cells with high levels of Dup also have elevated levels of Gem protein. (biologists.org)
  • The plasmid DNA encodes for multiple HLA-A2-restricted epitopes derived from the HPV-16 E7 protein, one of two HPV oncoproteins consistently expressed in neoplastic cells. (aacrjournals.org)

inhibitor

  • There is another inhibitor of rereplication that is unique to metazoa, Geminin (Gem), which is expressed during S, G2 and early M phases. (biologists.org)
  • To identify small molecular weight compounds with TGF-β-like activities, high throughput screening was performed using mink lung epithelial cells stably transfected with a TGF-β-responsive plasminogen activator inhibitor 1 promoter/luciferase construct. (aacrjournals.org)

apoptosis

  • Flow cytometric cell cycle analysis revealed that AQP4 knockout increased the basal apoptosis and induced a G2-M arrest in ANSCs. (biologists.org)

Mitotic

  • In addition, male myt1 germline cells occasionally undergo an extra mitotic division, resulting in meiotic cysts with twice the normal numbers of cells. (biologists.org)

vivo

  • Yet, few in vivo substrates linking CDK activity with the promotion of particular events in the cell cycle have been characterised. (biologists.org)

arrest

  • Because nearly half of all human tumors have abnormal p53 and thus are unable to arrest in G 1 following DNA damage, attention has primarily focused on the G 2 checkpoint ( 4 ). (aacrjournals.org)

progenitor

  • Although it is less common in mammals, some tissues - including heart muscle cells, platelet progenitor megakaryocytes, and liver parenchyma - develop a certain degree of polyploidy during their normal life cycle. (jci.org)

nuclear

  • We find that the size of individual muscles correlates with the number of nuclei per muscle cell and with increasing nuclear ploidy during development. (biologists.org)

CDC25A

  • The CDC25A (phospho T506) polyclonal antibody (Cat # PAB0430) is used in Western blot to detect Phospho-CDC25A-T506 in cells transfected with wild type or mutant T506A of CDC25A. (abnova.com)

mutations

  • In the current study, tumor cell lines and xenografts with p53 mutations were shown to be significantly radiosensitized with AZD7762 treatment, whereas normal fibroblasts were not. (aacrjournals.org)
  • Cells with mutations in either of the TGF-β receptors I or II were growth-arrested by A-161906. (aacrjournals.org)

stem cells

  • Aquaporin-4 (AQP4), a key molecule for maintaining water and ion homeostasis in the central nervous system, is expressed in adult neural stem cells (ANSCs) as well as astrocytes. (biologists.org)
  • In addition to providing structural and trophic supports for neurons, astrocytes are known to modulate the local environment around neural stem cells ( Doetsch, 2003 ). (biologists.org)

viability

  • Deletion of SLK19 , but not SPO12 , eliminated the mid-anaphase pause, caused premature anaphase onset and defects in DNA division during anaphase, and reduced viability in these cells. (biologists.org)

segregation

  • We propose that transient activation of the pre-anaphase checkpoint in kinesin-5-mutated cells induces a Slk19-dependent mid-anaphase pause, which might be important for proper DNA segregation. (biologists.org)

larval

  • Drosophila larval skeletal muscles are single, multinucleated cells of different sizes that undergo tremendous growth within a few days. (biologists.org)

dependent

  • We have previously shown that destruction of the Drosophila homolog of Cdt1, Double-parked (Dup), at G1-S is dependent upon cyclin-E/CDK2 and important to prevent re-replication and cell death. (biologists.org)

nucleolus

  • Cdc14 phosphatase is sequestered in the nucleolus during most of the cell cycle via its interaction with Cfi1 (also known as Net1), which is stabilized by Fob1 (reviewed in D'Amours and Amon, 2004 ). (biologists.org)

cytoplasm

requirement

  • however, the abrogation of the G 2 checkpoint was not an absolute requirement for AZD7762-mediated radiosensitization. (aacrjournals.org)

whereas

  • In contrast, impairment of insulin signaling drastically reduced the formation of binucleated tetraploid cells, whereas repeated insulin injections promoted the generation of these liver cells. (jci.org)
  • AV22EL exhibited no cytocidal effect on normal human colonic cells and hepatocytes, whereas these cells were eliminated by wild-type adenovirus. (aacrjournals.org)

temporal

  • Loss of the S-phase cyclin Clb5p under conditions of limited CDK activity ( cdc28-4 clb5 Δ cells) abolishes this temporal control and results in diploid-specific lethality. (biologists.org)

normal

  • AZD7762 treatment alone exhibited little cytotoxicity to any of the cell lines and did not enhance the radiosensitivity of normal human fibroblasts (1522). (aacrjournals.org)

primarily

  • Caffeine enhances the radiosensitivity of cells primarily through abrogation of the G 2 checkpoint ( 6 ). (aacrjournals.org)

injections

  • Each subject was treated with four i.m. injections of 50-400 μg of ZYC101 at 3-week intervals. (aacrjournals.org)

HUMAN

  • Survival of both p53 wild-type and mutant human cell lines was evaluated by clonogenic assay. (aacrjournals.org)

replication

  • We propose that, in cycling cells, Dup destruction is coupled to DNA replication and that increased levels of Gem balance elevated Dup levels to prevent pre-RC reformation when Dup degradation fails. (biologists.org)
  • Either under- or over-replication compromises genome integrity and can result in cell death or cancer. (biologists.org)
  • The targets of this regulation are origins of DNA replication, which are restricted to initiate replication only once per cell cycle. (biologists.org)

division

  • It functions during the seperation of chromosomes in cell division. (getrevising.co.uk)
  • To our knowledge, these results are the first demonstration in a physiological context that insulin signaling through Akt controls a specific cell division program and leads to the physiologic generation of binucleated tetraploid liver cells. (jci.org)
  • This can partly be attributed to ectopic division of germline-associated somatic cells in myt1 mutants, suggesting that Myt1 serves a role in regulating exit from the cell cycle. (biologists.org)

Targets

  • This asymmetric behaviour targets each pole to opposite compartments of the dividing cell. (biologists.org)

Lines

  • Using luciferase activity as a reporter gene, we showed that A33Pr was active in CRC cell lines. (aacrjournals.org)
  • Cell lines and tissue specimens. (aacrjournals.org)
  • AZD7762 treatment enhanced the radiosensitivity of p53-mutated tumor cell lines (DMFs ranging from 1.6-1.7) to a greater extent than for p53 wild-type tumor lines (DMFs ranging from 1.1-1.2). (aacrjournals.org)
  • There are several lines of evidence suggesting that the G 2 checkpoint can be exploited to enhance radiosensitivity. (aacrjournals.org)

anaphase

  • We found that, in kinesin-5-mutated cells, predominantly in kip1 Δ cin8-F467A cells, anaphase spindle elongation was frequently interrupted after the fast phase, resulting in a mid-anaphase pause. (biologists.org)
  • The mechanisms that control the transition between the fast and slow anaphase-B phases have not yet been elucidated. (biologists.org)

microtubules

  • It functions to propel the cell forward, using the contraction of the microtubules. (getrevising.co.uk)

Consistently

  • Consistently, satellite cells fuse to pre-existing skeletal muscles, increasing the number of nuclei and supporting hypertrophy ( Buckingham, 2006 ). (biologists.org)

affects

  • Along with these profound effects of TGF-β on the growth of cells, it also affects the way cells interact with their environment through modulation of the extracellular matrix ( 4 ). (aacrjournals.org)

regulatory

  • Therefore, several regulatory mechanisms have evolved to ensure that the genome is completely replicated with high fidelity exactly once each cell cycle. (biologists.org)

specific

  • The signal transduced by these receptors produces a multitude of effects that are cell type specific. (aacrjournals.org)

mutant

  • Notably, more proliferating cells were observed in myt1 mutant testes and ovaries than controls. (biologists.org)

Species

  • Although InR/Tor signaling, Foxo and Myc have been causally associated with the growth of most cell types across species, how organ and body growth are in turn determined is still unclear. (biologists.org)

cancer

  • Patients living with this form of advanced head and neck cancer often experience debilitating physiological effects as well as emotional and social challenges brought on by the condition despite current treatment options," said Kevin Harrington, M.D., Ph.D., Professor in Biological Cancer Therapies at The Institute of Cancer Research, London, and a Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust in London. (businesswire.com)

allow

  • It functions to allow the movement of substances along the cell surface. (getrevising.co.uk)