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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
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.
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).
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.
The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
Agents that inhibit PROTEIN KINASES.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
The process by which a DNA molecule is duplicated.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
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.
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.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
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.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
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.
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.
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.
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.
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.
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.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
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.
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.
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.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A cell line derived from cultured tumor cells.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
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.
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.
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.
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.
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.
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.
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.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
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.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
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.
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.
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.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
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.
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.
Proteins found in any species of fungus.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Deoxyribonucleic acid that makes up the genetic material of fungi.
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.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
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.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
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.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
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.
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.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
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)
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
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.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
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.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
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)
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.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear 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.
The phosphoric acid ester of serine.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
Compounds that inhibit cell production of DNA or RNA.
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.
An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. It mediates proper CHROMOSOME SEGREGATION and contractile ring function during CYTOKINESIS.
Human COLORECTAL CARCINOMA cell line.
Transport proteins that carry specific substances in the blood or across cell membranes.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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).
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 enzymes
Proteins prepared by recombinant DNA technology.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
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.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
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)
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.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
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.
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.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
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.
Elements of limited time intervals, contributing to particular results or situations.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
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.
Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.
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.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
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.
A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
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.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
The rate dynamics in chemical or physical systems.
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).
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.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
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.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
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.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
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.
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.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
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.
The functional hereditary units of FUNGI.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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.
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)
The relationship between the dose of an administered drug and the response of the organism to the drug.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
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.-.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
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.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

A novel genetic screen for snRNP assembly factors in yeast identifies a conserved protein, Sad1p, also required for pre-mRNA splicing. (1/1039)

The assembly pathway of spliceosomal snRNPs in yeast is poorly understood. We devised a screen to identify mutations blocking the assembly of newly synthesized U4 snRNA into a functional snRNP. Fifteen mutant strains failing either to accumulate the newly synthesized U4 snRNA or to assemble a U4/U6 particle were identified and categorized into 13 complementation groups. Thirteen previously identified splicing-defective prp mutants were also assayed for U4 snRNP assembly defects. Mutations in the U4/U6 snRNP components Prp3p, Prp4p, and Prp24p led to disassembly of the U4/U6 snRNP particle and degradation of the U6 snRNA, while prp17-1 and prp19-1 strains accumulated free U4 and U6 snRNA. A detailed analysis of a newly identified mutant, the sad1-1 mutant, is presented. In addition to having the snRNP assembly defect, the sad1-1 mutant is severely impaired in splicing at the restrictive temperature: the RP29 pre-mRNA strongly accumulates and splicing-dependent production of beta-galactosidase from reporter constructs is abolished, while extracts prepared from sad1-1 strains fail to splice pre-mRNA substrates in vitro. The sad1-1 mutant is the only splicing-defective mutant analyzed whose mutation preferentially affects assembly of newly synthesized U4 snRNA into the U4/U6 particle. SAD1 encodes a novel protein of 52 kDa which is essential for cell viability. Sad1p localizes to the nucleus and is not stably associated with any of the U snRNAs. Sad1p contains a putative zinc finger and is phylogenetically highly conserved, with homologues identified in human, Caenorhabditis elegans, Arabidospis, and Drosophila.  (+info)

Caffeine can override the S-M checkpoint in fission yeast. (2/1039)

The replication checkpoint (or 'S-M checkpoint') control prevents progression into mitosis when DNA replication is incomplete. Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells. We show here that caffeine also disrupts the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. By contrast, no comparable effects of caffeine on the S. pombe DNA damage checkpoint were seen. S. pombe cells arrested in early S phase and then exposed to caffeine lost viability rapidly as they attempted to enter mitosis, which was accompanied by tyrosine dephosphorylation of Cdc2. Despite this, the caffeine-induced loss of viability was not blocked in a temperature-sensitive cdc2 mutant incubated at the restrictive temperature, although catastrophic mitosis was prevented under these conditions. This suggests that, in addition to S-M checkpoint control, a caffeine-sensitive function may be important for maintenance of cell viability during S phase arrest. The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint control and recovery from S phase arrest. In addition, the same combination of drugs was specifically tolerated in cells overexpressing either of two novel S. pombe genes isolated in a cDNA library screen. These findings should allow further molecular investigation of the regulation of S phase arrest, and may provide a useful system with which to identify novel drugs that specifically abrogate the checkpoint control.  (+info)

RAD53 regulates DBF4 independently of checkpoint function in Saccharomyces cerevisiae. (3/1039)

The Cdc7p and Dbf4p proteins form an active kinase complex in Saccharomyces cerevisiae that is essential for the initiation of DNA replication. A genetic screen for mutations that are lethal in combination with cdc7-1 led to the isolation of seven lsd (lethal with seven defect) complementation groups. The lsd7 complementation group contained two temperature-sensitive dbf4 alleles. The lsd1 complementation group contained a new allele of RAD53, which was designated rad53-31. RAD53 encodes an essential protein kinase that is required for the activation of DNA damage and DNA replication checkpoint pathways, and that is implicated as a positive regulator of S phase. Unlike other RAD53 alleles, we demonstrate that the rad53-31 allele retains an intact checkpoint function. Thus, the checkpoint function and the DNA replication function of RAD53 can be functionally separated. The activation of DNA replication through RAD53 most likely occurs through DBF4. Two-hybrid analysis indicates that the Rad53p protein binds to Dbf4p. Furthermore, the steady-state level of DBF4 message and Dbf4p protein is reduced in several rad53 mutant strains, indicating that RAD53 positively regulates DBF4. These results suggest that two different functions of the cell cycle, initiation of DNA replication and the checkpoint function, can be coordinately regulated through the common intermediate RAD53.  (+info)

A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. (4/1039)

Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. Much of our current understanding of checkpoints comes from genetic studies conducted in yeast. In the fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component of both the DNA damage and DNA replication checkpoints. The SpChk1 and SpCds1 protein kinases function downstream of SpRad3. SpChk1 is an effector of the DNA damage checkpoint and, in the absence of SpCds1, serves an essential function in the DNA replication checkpoint. SpCds1 functions in the DNA replication checkpoint and in the S phase DNA damage checkpoint. Human homologs of both SpRad3 and SpChk1 but not SpCds1 have been identified. Here we report the identification of a human cDNA encoding a protein (designated HuCds1) that shares sequence, structural, and functional similarity to SpCds1. HuCds1 was modified by phosphorylation and activated in response to ionizing radiation. It was also modified in response to hydroxyurea treatment. Functional ATM protein was required for HuCds1 modification after ionizing radiation but not after hydroxyurea treatment. Like its fission yeast counterpart, human Cds1 phosphorylated Cdc25C to promote the binding of 14-3-3 proteins. These findings suggest that the checkpoint function of HuCds1 is conserved in yeast and mammals.  (+info)

Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. (5/1039)

In the fission yeast Schizosaccharomyces pombe, the protein kinase Cds1 is activated by the S-M replication checkpoint that prevents mitosis when DNA is incompletely replicated. Cds1 is proposed to regulate Wee1 and Mik1, two tyrosine kinases that inhibit the mitotic kinase Cdc2. Here, we present evidence from in vivo and in vitro studies, which indicates that Cds1 also inhibits Cdc25, the phosphatase that activates Cdc2. In an in vivo assay that measures the rate at which Cdc25 catalyzes mitosis, Cds1 contributed to a mitotic delay imposed by the S-M replication checkpoint. Cds1 also inhibited Cdc25-dependent activation of Cdc2 in vitro. Chk1, a protein kinase that is required for the G2-M damage checkpoint that prevents mitosis while DNA is being repaired, also inhibited Cdc25 in the in vitro assay. In vitro, Cds1 and Chk1 phosphorylated Cdc25 predominantly on serine-99. The Cdc25 alanine-99 mutation partially impaired the S-M replication and G2-M damage checkpoints in vivo. Thus, Cds1 and Chk1 seem to act in different checkpoint responses to regulate Cdc25 by similar mechanisms.  (+info)

Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. (6/1039)

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.  (+info)

Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases. (7/1039)

Six checkpoint Rad proteins (Rad1, Rad3, Rad9, Rad17, Rad26, and Hus1) are needed to regulate checkpoint protein kinases Chk1 and Cds1 in fission yeast. Chk1 is required to prevent mitosis when DNA is damaged by ionizing radiation (IR), whereas either kinase is sufficient to prevent mitosis when DNA replication is inhibited by hydroxyurea (HU). Checkpoint Rad proteins are required for IR-induced phosphorylation of Chk1 and HU-induced activation of Cds1. IR activates Cds1 only during the DNA synthesis (S) phase, whereas HU induces Chk1 phosphorylation only in cds1 mutants. Here, we investigate the basis of the checkpoint signal specificity of Chk1 phosphorylation and Cds1 activation. We show that IR fails to induce Chk1 phosphorylation in HU-arrested cells. Release from the HU arrest following IR causes substantial Chk1 phosphorylation. These and other data indicate that Cds1 prevents Chk1 phosphorylation in HU-arrested cells, which suggests that Cds1 actively suppresses a repair process that leads to Chk1 phosphorylation. Cds1 becomes more highly concentrated in the nucleus only during the S phase of the cell cycle. This finding correlates with S-phase specificity of IR-induced activation of Cds1. However, constitutive nuclear localization of Cds1 does not enhance IR-induced activation of Cds1. This result suggests that Cds1 activation requires DNA structures or protein activities that are present only during S phase. These findings help to explain how Chk1 and Cds1 respond to different checkpoint signals.  (+info)

RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. (8/1039)

Eukaryotic checkpoint genes regulate multiple cellular responses to DNA damage. In this report, we examine the roles of budding yeast genes involved in G2/M arrest and tolerance to UV exposure. A current model posits three gene classes: those encoding proteins acting on damaged DNA (e.g. RAD9 and RAD24), those transducing a signal (MEC1, RAD53 and DUN1) or those participating more directly in arrest (PDS1). Here, we define important features of the pathways subserved by those genes. MEC1, which we find is required for both establishment and maintenance of G2/M arrest, mediates this arrest through two parallel pathways. One pathway requires RAD53 and DUN1 (the 'RAD53 pathway'); the other pathway requires PDS1. Each pathway independently contributes approximately 50% to G2/M arrest, effects demonstrable after cdc13-induced damage or a double-stranded break inflicted by the HO endonuclease. Similarly, both pathways contribute independently to tolerance of UV irradiation. How the parallel pathways might interact ultimately to achieve arrest is not yet understood, but we do provide evidence that neither the RAD53 nor the PDS1 pathway appears to maintain arrest by inhibiting adaptation. Instead, we think it likely that both pathways contribute to establishing and maintaining arrest.  (+info)

Duplication of a cells genetic material is of paramount importance. This task must be completed accurately, efficiently and occur once and only once within any given cell cycle. Origin firing, which occurs according to a temporal program, results in the establishment of bidirectional replication forks. As replication forks traverse the chromosomal landscape, their stability is threatened by endogenous obstacles such as heavily transcribed tRNAs, protein-DNA complexes and replication slow zones. In addition, fork stability can also be threatened by genotoxic agents. During S phase, in response to genotoxin-induced stress, the cell activates the intra-S phase checkpoint. The intra-S phase checkpoint is comprised of three major groups of proteins: sensors, adaptors and effectors. Sensor proteins detect problems at the replication fork and elicit a phosphorylation cascade that is mediated by adaptor proteins and results in the activation of effector kinases. Together, these proteins act to ...
Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second Chk2 molecule, promoting dimerisation of the protein and triggering phosphorylation of the activation segment/T-loop in the kinase domain. We have now determined the structure of the kinase domain of human Chk2 in complexes with ADP and a small-molecule inhibitor debromohymenialdisine. The structure reveals a remarkable dimeric arrangement in which T-loops are exchanged between protomers, to form an active kinase conformation in trans. Biochemical data suggest that this dimer is the biologically active state promoted by ATM-phosphorylation, and also suggests a mechanism for dimerisation-driven activation of Chk2 by ...
TY - JOUR. T1 - Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase. AU - Jin, Jianping. AU - Cambronne, Xiaolu. AU - Ye, Xin. AU - Livingstone, Mark. AU - Harper, J. Wade. PY - 2008/7/11. Y1 - 2008/7/11. N2 - In response to DNA damage, cells activate a signaling pathway that promotes cell cycle arrest and degradation of the cell cycle regulator Cdc25A. Cdc25A degradation occurs via the SCFβ-TRCP pathway and phosphorylation of Ser-76. Previous work indicates that the checkpoint kinase Checkpoint kinase 1 (Chk1) is capable of phosphorylating Ser-76 in Cdc25A, thereby promoting its degradation. In contrast, other experiments involving overexpression of dominant Chk2 mutant proteins point to a role for Chk2 in Cdc25A degradation. However, loss-of-function studies that implicate Chk2 in Cdc25A turnover are lacking, and there is no evidence that Chk2 is capable of phosphorylating Ser-76 in Cdc25A despite the finding that Chk1 and Chk2 ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010 ...
TY - JOUR. T1 - CHEK2 variant I157T may be associated with increased breast cancer risk. AU - Kilpivaara, Outi. AU - Vahteristo, Pia. AU - Falck, Jacob. AU - Syrjäkoski, Kirsi. AU - Eerola, Hannaleena. AU - Easton, Douglas. AU - Bartkova, Jirina. AU - Lukas, Jiri. AU - Heikkilä, Päivi. AU - Aittomäki, Kristiina. AU - Holli, Kaija. AU - Blomqvist, Carl. AU - Kallioniemi, Olli. AU - Bartek, Jiri. AU - Nevanlinna, Heli. PY - 2004. Y1 - 2004. N2 - Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to DNA damage. The CHEK2 1100delC has previously been shown to be a low‐penetrance breast cancer susceptibility allele. We have evaluated the role of another CHEK2 variant, I157T in the FHA domain of the gene, for association with breast cancer. I157T was found at a significantly higher frequency in the population‐based series of breast cancer patients (77/1035, 7.4%, odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.06-1.95, p = 0.021) than among population ...
Although overexpression of multiple ATP-binding cassette transporters has been reported in clinical samples, few studies have examined how coexpression of multiple transporters affected resistance to chemotherapeutic drugs. We therefore examined how coexpression of ABCB1 (P-glycoprotein) and ABCG2 contributes to drug resistance in a cell line model. HEK293 cells were transfected with vector-encoding full-length ABCB1, ABCG2, or a bicistronic vector containing both genes, each under the control of a separate promoter. Cells transfected with both transporters (B1/G2 cells) demonstrated high levels of both transporters, and uptake of both the ABCB1-specific substrate rhodamine 123 and the ABCG2-specific substrate pheophorbide a was reduced when examined by flow cytometry. B1/G2 cells were also cross-resistant to the ABCB1 substrate doxorubicin, the ABCG2 substrate topotecan, as well as mitoxantrone and the cell cycle checkpoint kinase 1 inhibitor prexasertib, both of which were found to be ...
Recombinant Checkpoint Kinase 1 (CHEK1) Protéine. Origine: Humain. Source: Baculovirus infected Insect Cells. Commandez ABIN457519.
ProNAi Therapeutics has obtained an exclusive license from the CRT Pioneer Fund for worldwide rights to develop and commercialize PNT737, a small-molecule inhibitor of checkpoint kinase 1 (Chk1)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with EMD- (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page ...
Inhibition of ATR (a DNA damage checkpoint kinase) is currently being evaluated with radiotherapy and chemoradiation in patients with oesophageal cancer in the Cancer Research UK/MRC funded CHARIOT clinical study, whilst dose escalation is being evaluated in the SCOPE 2 clinical study. We have done initial in silico planning to show that protons significantly reduce the dose received by heart and lung and dose modelling to predict toxicity of dose escalation. Furthermore we have shown that heart substructures have a critical role in non-cancer related mortality.
CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Its potential as a drug target is still unclear, but inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies in a p53 mutant background by eliminating one of the checkpoints or DNA repair pathways contributing to cellular resistance. We report here the identification and characterization of a novel CHK2 kinase inhibitor, CCT241533. X-ray crystallography confirmed that CCT241533 bound to CHK2 in the ATP pocket. This compound inhibits CHK2 with an IC50 of 3 nmol/L and shows minimal cross-reactivity against a panel of kinases at 1 mu mol/L. CCT241533 blocked CHK2 activity in human tumor cell lines in response to DNA damage, as shown by inhibition of CHK2 autophosphorylation at S516, band shift mobility changes, and HDMX degradation. CCT241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, this compound significantly potentiates the ...
TY - JOUR. T1 - Phosphorylation of human Rad9 is required for genotoxin-activated checkpoint signaling. AU - Roos-Mattjus, Pia. AU - Hopkins, KM. AU - Oestreich, AJ. AU - Vroman, BT. AU - Johnson, KL. AU - Naylor, S. AU - Lieberman, HB. AU - Karnitz, LM. PY - 2003. Y1 - 2003. N2 - Rad9, a key component of genotoxin-activated checkpoint signaling pathways, associates with Hus1 and Rad1 in a heterotrimeric complex (the 9-1-1 complex). Rad9 is inducibly and constitutively phosphorylated. However, the role of Rad9 phosphorylation is unknown. Here we identified nine phosphorylation sites, all of which lie in the carboxyl-terminal 119-amino acid Rad9 tail and examined the role of phosphorylation in geno-toxin-triggered checkpoint activation. Rad9 mutants lacking a Ser-272 phosphorylation site, which is phosphorylated in response to genotoxins, had no effect on survival or checkpoint activation in Mrad9(-/-) mouse ES cells treated with hydroxyurea (HU), ionizing radiation (IR), or ultraviolet radiation ...
Cdc7 and CK1g1 independently and additively phosphorylate the Chk1-binding domain of claspin to activate replication checkpoint with differential contribution of each kinase in different cell types.
BCR-ABL+ B-ALL is only transiently responsive to current therapies (29), with a 5-y survival of ∼35% (30, 31). Given this low survival rate, additional therapies are needed. One approach that has not been well explored in this disease is checkpoint blockade-based immunotherapy. Checkpoint blockade works well in malignancies with many nonsynonymous mutations and can lead to improved long-term survival in patients with such cancers (4, 32-36). Presumably, this is because the increased number of nonsynonymous mutations allows for a concurrent increase in the number of neoantigen-specific T cells. Comparatively, in cancers with low numbers of nonsynonymous mutations, such as B-ALL (36), checkpoint blockade-based immunotherapy targeting the endogenous immune response is relatively unstudied. In fact, current paradigms suggest that cancers with low numbers of nonsynonymous mutations may not be effectively treated using anti-CTLA4 and anti-PD1 checkpoint blockade (35). In the present study, we show ...
Mouse anti Human Chk2 antibody, clone 4B7 recognizes human Serine/threonine-protein kinase Chk2, also known as Chk2, CHK2 checkpoint homol
The checkpoint kinases Chk1/Chk2 and the CDK inhibitor p21 are known to have important complementary roles in this process, in G2 arrest and cell cycle exit, respectively ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
View Notes - Week 3 Checkpoint Fiber Research from SCI/241 AAGH0JAD35 at University of Phoenix. Week 3 Checkpoint: Fiber Research What is the function of fiber in the body? Fiber assists the body in
CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer.
Only do checkpoint, when the PVMs and SVMs output net packets are inconsistent, We also limit the min time between two continuous checkpoint action, to give VM a change to run. Signed-off-by: zhanghailiang ,[email protected], Signed-off-by: Li Zhijian ,[email protected], --- include/net/colo-nic.h , 2 ++ migration/colo.c , 32 ++++++++++++++++++++++++++++++++ net/colo-nic.c , 5 +++++ 3 files changed, 39 insertions(+) diff --git a/include/net/colo-nic.h b/include/net/colo-nic.h index 809726c..57c6719 100644 --- a/include/net/colo-nic.h +++ b/include/net/colo-nic.h @@ -20,4 +20,6 @@ void colo_proxy_destroy(enum colo_mode mode); void colo_add_nic_devices(NetClientState *nc); void colo_remove_nic_devices(NetClientState *nc); +int colo_proxy_compare(void); + #endif diff --git a/migration/colo.c b/migration/colo.c index 22d7df1..a7cead9 100644 --- a/migration/colo.c +++ b/migration/colo.c @@ -17,6 +17,13 @@ #include migration/migration-failover.h #include net/colo-nic.h +/* +* We should not do ...
4A9S: Benzimidazole Inhibitors of the Protein Kinase Chk2: Clarification of the Binding Mode by Flexible Side Chain Docking and Protein-Ligand Crystallography.
Finden Sie alle Bücher von Herausgegeben von Schönthal, Axel H. - Checkpoint Controls and Cancer. Bei der Büchersuchmaschine eurobuch.com können Sie antiquarische und Neubücher VERGLEICHEN UND SOFORT zum Bestpreis bestellen. 1617374261
CCT244747 is a potent, orally bioavailable and highly selective CHK1 inhibitor, with an IC50 of 7.7 nM; CCT244747 also abrogates G2 checkpoint with an IC50 of 29 nM ...
Choose Frequencies from the Calculation drop down. Processors as 1. Theory as B3LYP. 6-31G(d) as Basis set. Charge zero. Multiplicity 1. Output as Standard. Format as cartesian Check the checkpoint check box. ...
The cellular response to DNA damage is critical for maintenance of genomic integrity and inhibition of tumorigenesis. Mutations or aberrant expression of the E3 ubiquitin ligase EDD have been observed in a number of carcinomas and we recently reported that EDD modulates activity of the DNA damage checkpoint kinase, CHK2. Here, we demonstrate that EDD is necessary for G(1)/S and intra S phase DNA damage checkpoint activation and for the maintenance of G(2)/M arrest after double strand DNA breaks. Defective checkpoint activation in EDD-depleted cells led to radio-resistant DNA synthesis, premature entry into mitosis, accumulation of polyploid cells, and cell death via mitotic catastrophe. In addition to decreased CHK2 activation in EDD-depleted cells, the expression of several key cell cycle mediators including Cdc25A/C and E2F1 was altered, suggesting that these checkpoint defects may be both CHK2-dependent and -independent. These data support a role for EDD in the maintenance of genomic stability,
This dataset is the original data files (Western blot, FACS etc.) for the article Helicase subunit Cdc45 targets the checkpoint kinase Rad53 to both replication initiation and elongation complexes after fork stalling, publishing in Molecular Cell.
The DNA replication checkpoint is a complex signal transduction pathway, present in all eukaryotic cells, that functions to maintain genomic integrity and cell viability when DNA replication is perturbed. In Schizosaccharomyces pombe the major effector of the replication checkpoint is the protein kinase Cds1. Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator Mrc1, but the biochemical mechanism of activation is not well understood. We report that the replication checkpoint is activated in two stages. In the first stage, Mrc1 recruits Cds1 to stalled replication forks by interactions between the FHA domain of Cds1 and specific phosphorylated Rad3 consensus sites in Mrc1. Cds1 is then primed for activation by Rad3-dependent phosphorylation. In the second stage, primed Cds1 molecules dimerize via phospho-specific interactions mediated by the FHA domains and are activated by autophosphorylation. This two-stage activation mechanism for the replication checkpoint allows for rapid
TY - JOUR. T1 - Undamaged DNA transmits and enhances DNA damage checkpoint signals in early embryos. AU - Peng, Aimin. AU - Lewellyn, Andrea L.. AU - Maller, James L.. PY - 2007/10/1. Y1 - 2007/10/1. N2 - In Xenopus laevis embryos, the midblastula transition (MBT) at the 12th cell division marks initiation of critical developmental events, including zygotic transcription and the abrupt inclusion of gap phases into the cell cycle. Interestingly, although an ionizing radiation-induced checkpoint response is absent in pre-MBT embryos, introduction of a threshold amount of undamaged plasmid or sperm DNA allows a DNA damage checkpoint response to be activated. We show here that undamaged threshold DNA directly participates in checkpoint signaling, as judged by several dynamic changes, including H2AX phosphorylation, ATM phosphorylation and loading onto chromatin, and Chk1, Chk2 phosphorylation and release from nuclear DNA. These responses on physically separate threshold DNA require γ-H2AX and are ...
VANCOUVER, Sept. 27, 2016- ProNAi Licenses Oncology Drug Targeting DNA Damage Response Checkpoint Kinase 1 (Chk1) from CRT Pioneer Fund, UK.
Although p53-deficiency is a common factor in many cancers and loss of p53 activity contributes to the inappropriate survival of cells that have DNA damage, in vitro studies suggest that there are p53-independent cell death pathways. To facilitate the discovery of such p53-independent pathways, Sidi et al. targeted kinases involved in the DNA damage response with morpholino antisense oligonucleotides in zebrafish embryos defective for p53 activity and found that when the kinase Chk1 was knocked down, cell death (detected with acridine orange) due to irradiation was restored to that of wild-type embryos exposed to irradiation. A specific inhibitor of Chk1 (Gö6976), but not inhibitors for the DNA damage checkpoint kinases ATM or Chk2, also restored irradiation-induced cell death in p53-deficient zebrafish embryos. Although the morphological and ultrastructural characteristics of apoptosis were present in the irradiated p53e7/e7;chk1MO embryos (DNA fragmentation, chromatin compaction, and ...
PMID 17517688] Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case-control study. [PMID 17508290] Genetic susceptibility to breast cancer. [PMID 17458694] Detection of the CHEK2 1100delC mutation by MLPA BRCA1/2 analysis: a worthwhile strategy for its clinical applicability in 1100delC low-frequency populations? [PMID 17428325] Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. [PMID 17428320] Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study. ...
Rad9 functions in the DNA-damage checkpoint pathway of Saccharomyces cerevisiae. In whole-cell extracts, Rad9 is found in large, soluble complexes, which have functions in amplifying the checkpoint signal. The two main soluble forms of Rad9 complexes that are found in cells exposed to DNA-damaging treatments were purified to homogeneity. Both of these Rad9 complexes contain the Ssa1 and/or Ssa2 chaperone proteins, suggesting a function for these proteins in checkpoint regulation. Consistent with this possibility, genetic experiments indicate redundant functions for SSA1 and SSA2 in survival, G2/M-checkpoint regulation, and phosphorylation of both Rad9 and Rad53 after irradiation with ultraviolet light. Ssa1 and Ssa2 can now be considered as novel checkpoint proteins that are likely to be required for remodelling Rad9 complexes during checkpoint-pathway activation.
Schuler, F., Afreen, S., Manzl, C., Häcker, G., Erlacher, M.,Villunger, A. Checkpoint kinase 1 is essential for fetal and adult hematopoiesis. EMBO Reports. 2019; e47026. doi:10.15252/embr.201847026. ...
Conducting regular sobriety checkpoints can significantly reduce crashes that involve drivers who have consumed alcohol. This is the major finding of an international review by the Centers for Disease Control of 23 studies of checkpoints. The researchers found that checkpoints reduce alcohol-related crashes and associated fatal and nonfatal injuries ... . Despite differences across studies in design, periods of observation, and outcome measures evaluated, the results were generally consistent in direction and size.. Sobriety checkpoints reduced the crashes involving alcohol by about 20 percent, the researchers found. They pointed to the effectiveness of checkpoints that were conducted at the city, state, and national levels. Checkpoints conducted on both urban and rural roads were effective, the CDC reported.. The researchers reviewed studies of two types of checkpoints - those involving random breath tests at which every driver passing through is tested and those at which police must have a ...
Excess Hsl7 overrides the DNA replication checkpoint. (A) Xenopus Hsl7 or β-globin mRNA was incubated in cycling extracts in the presence of aphidicolin (200
Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells.
Cells use biochemical signaling mechanisms known as checkpoints to monitor the status of the cell so that cell division occurs only when conditions allow for successful mitosis. One such checkpoint allows cell division to occur only if DNA replication is complete and no active replication forks are present. However, Torres-Rosell et al. (see the Perspective by Weinert) describe experiments in which uncompleted replication of ribosomal DNA (rDNA) genes does not prevent cells from proceeding into anaphase. Thus, at least in the scenario studied, in which yeast bear mutations in the genes encoding the Smc5 and Smc6 proteins (which function as a heterodimer in DNA repair), the delayed replication of rDNA did not trigger a checkpoint that blocks progression of the cells into mitosis.. J. Torres-Rosell, G. De Piccoli, V. Cordon-Preciado, S. Farmer, A. Jarmuz, F. Machin, P. Pasero, M. Lisby, J. E. Haber, L. Aragón, Anaphase onset before complete DNA replication with intact checkpoint responses. ...
with ATM or ATR activation leads to induction of p21Waf1 and cell loss of life in the jnk2 knockout cells. We then centered our studies more closely on the DNA replication element CDT1. CDT1 expression is essential for replication fork development throughout S period. Geminin inhibits CDT1 to stall replication forks and allow G2/M transit. CDT1 degradation by proteases also facilitates this procedure. Lack of CDT1 inhibition/degradation or overexpression of CDT1 results in re-replication in some mobile strains. In other mobile strains, mobile cycle examine factors inhibit re-replication by activating ATR/Chk1 responses. Collapsed replication forks or overt re-replication can direct to double strand breaks. ATM/p53 induction and increased p21Waf1 expression are responses that stop or restore DNA hurt [24]. As in preceding reports, cells have been serum starved and then stimulated with FBS. Endogenous Similarly, CDT1 expression was evaluated in a time dependent trend alongside with p53 Ser15 ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
This mapping shows where the WCAG 1.0 checkpoints appear in the 16 June 2003 Working Draft. The WCAG 2.0 Working Draft is prepared by the Web Content Accessibility Guidelines Working Group (WCAG WG) to show how more generalized (less HTML-specific) WCAG checkpoints might read. The Working Draft is not based on consensus of the WCAG Working Group nor has it gone through W3C process. Checkpoints in the WCAG 2.0 Working Draft in no way supersede the checkpoints in WCAG 1.0.. The Web Content Accessibility Guidelines Working Group is working carefully to enable organizations and individuals that are currently using WCAG 1.0 (which remains stable and referenceable at this time) to ensure that they will eventually be able to make a smooth transition to WCAG 2.0.. ...
Now, what factors affect checkpoint_age? When we execute queries that change pages (i.e., INSERT/UPDATE/DELETE), we perform writes to the log, we change pages, and checkpoint_age is growing. When we perform flushing of changed pages, checkpoint_age is going down.. So that means the main way we have to keep checkpoint_age within point T is to change the number of pages being flushed per second. That way, we can keep checkpoint_age down.. If this doesnt help-and checkpoint_age keeps growing beyone T toward async-we have a second control mechanism: We can add a delay into INSERT/UPDATE/DELETE operations. This way we prevent checkpoint_age from growing and reaching async.. To summarize, the idea of our algorithm is : We keep checkpoint_age within point T by increasing or decreasing the number of pages flushed per second. If checkpoint_age continues to grow, we add throttling to prevent it. The throttling depends on the position of checkpoint_age - the closer to async, the bigger the ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
ALPS Checkpoint is a Statutory board located in Changi. A number of Government Agency and others business can be found in ALPS Checkpoint.
TSA to Evaluate Optosecurity Solutions for Checkpoint Screening and Management : TSA to Evaluate Optosecurity SolutionsTSA to Evaluate Optosecurity Solutions for Checkpoint Screening and Management PR Newswire WASHINGTON, November 4, 2013 In its continuing effort to identify, evaluate, and implement risk-based security solutions, the Department of
The entire event will be in the dark with a mixture of street and off road route options. It is perfect for those wanting to get prepared for the Spring Challenge at the end of September. Come along and bring your friends! These fun 2hour rogaine is suitable for gurus to newbies. Anybody that has a moderate level of fitness can participate. A high level of navigation ability is not required.. Rogaining involves teams of two to five members visit as many checkpoints as possible in the time allowed. Shorter duration rogaines often allow solo competitors. Checkpoints are scored differently depending on level of difficulty in reaching them; therefore teams choose a strategy (for example, to visit many low score checkpoints)and route selection becomes a vital component.. Teams travel entirely on foot, navigating by map and compass between checkpoints in terrain that varies from open farmland to hilly forest. Teams travel at their own pace and anyone from children to grandparents can experience the ...
Chk1 (phospho Ser317) antibody (checkpoint kinase 1) for ICC/IF, WB. Anti-Chk1 (phospho Ser317) pAb (GTX132170) is tested in Human samples. 100% Ab-Assurance.
In this new paper by Nir Hacohen et al., researchers found that by analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, they found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system.
Weight training involves a lot of focus and attention. Learn five full body checkpoints for weight lifting that you can check on your own.
Edison, NJ (PRWEB) May 14, 2008 -- CheckPoint HR, LLC, an innovator and leading Administrative Service Organization (ASO) (http://www.checkpointhr.com/hrms/)
Plasmid pDONR223-CHEK2 from Dr. William Hahns lab contains the insert CHEK2 and is published in Nature. 2010 Nov 24. ():. This plasmid is available through Addgene.
The first thing to remember, and a surefire way to not get a DUI, is Dont drive after drinking. Call a taxi; use Uber, Lyft, or a similar service; or have a designated driver. If you do find yours
Providing surgeons with state-of-the-art neurodevices to locate and identify nerves and evaluate nerve and muscle excitability in surgical procedures. ...
CHIR-124 is a novel and potent Chk1 inhibitor with IC50 of 0.3 nM. It shows 2,000-fold selectivity against Chk2, 500- to 5,000-fold less activity agai...Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
Circulation 2000; 1021027-32. 12 Checkpoints Regulate Transition Events in a Network The cycle of cell growth and division passes through four stages (Figure 14.
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Heavy consumption of the essential amino acid lysine (as indicated in the treatment of cold sores) has allegedly shown false positives in some and was cited by American shotputter C. J. Hunter as the reason for his positive test, though in 2004 he
"Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1". Oncogene. England. 22 (48): 7593-9. doi: ... "Synucleins are a novel class of substrates for G protein-coupled receptor kinases". J. Biol. Chem. 275 (34): 26515-22. doi: ... 5 (6): 401-2. doi:10.1093/dnares/5.6.401. PMID 10048491. Surguchov A, Surgucheva I, Solessio E, Baehr W (1999). "Synoretin--A ... 13 (2): 95-103. doi:10.1006/mcne.1999.0735. PMID 10192768. S2CID 25249400. Duda JE, Shah U, Arnold SE, et al. (2000). "The ...
"Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1". Chromosoma. 113 (1): 1-15. ... Martin-Lluesma S, Stucke VM, Nigg EA (September 2002). "Role of Hec1 in spindle checkpoint signaling and kinetochore ... Meraldi P, Draviam VM, Sorger PK (July 2004). "Timing and checkpoints in the regulation of mitotic progression". Developmental ... HEC is one of several proteins involved in spindle checkpoint signaling. This surveillance mechanism assures correct ...
"Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1". Chromosoma. 113 (1): 1-15. ... 2004). "Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores". Curr. Biol. 13 (23 ... Meraldi P, Draviam VM, Sorger PK (2004). "Timing and checkpoints in the regulation of mitotic progression". Dev. Cell. 7 (1): ... 2004). "Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model". ...
"Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1". Molecular and Cellular Biology. 20 ( ... "Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Boddy MN, Lopez-Girona A, Shanahan P, Interthal H, Heyer WD ... 625 (1-2): 1-19. doi:10.1016/j.mrfmmm.2007.04.007. PMC 2100401. PMID 17555773. Nomura Y, Adachi N, Koyama H (Oct 2007). "Human ...
"Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases". Proceedings of the National ... As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S ... In late G1/early S phase, the pre-RC is activated for DNA unwinding by the cyclin-dependent kinases (CDKs) and DDK. This ... Upon entry into S phase, the activity of the CDKs and the Dbf4-dependent kinase (DDK) Cdc7 promotes the assembly of replication ...
Nigg, Erich A. (2001). "Mitotic kinases as regulators of cell division and its checkpoints". Nature Reviews Molecular Cell ... Serine/threonine-protein kinase 12, AIK2, AIM1, ARK2, STK12) Aurora-C (Serine/threonine-protein kinase 13, AIE2, AIK3, STK13) ... an Oncogenic Serine/Threonine Kinase J. Biol. Chem., (2002) 277: pp.42419-22 Aurora-A (Serine/threonine-protein kinase 6, AIK, ... Aurora kinases regulate cell cycle transit from G2 through cytokinesis and, thus, are targets in cancer therapy. There are ...
Cayrol C, Cougoule C, Wright M (Nov 2002). "The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase ... Cayrol C, Cougoule C, Wright M (Nov 2002). "The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase ... AP-2 complex subunit beta is a protein that in humans is encoded by the AP2B1 gene. The protein encoded by this gene is one of ... 73 (2): 1350-61. doi:10.1128/JVI.73.2.1350-1361.1999. PMC 103959. PMID 9882340. Owen DJ, Vallis Y, Pearse BM, McMahon HT, Evans ...
Pregueiro AM, Liu Q, Baker CL, Dunlap JC, Loros JJ (2006). "The Neurospora checkpoint kinase 2: a regulatory link between the ... and a calcium/calmodulin-dependent kinase (CAMK-1), and additional kinases, reaching its peak around mid-subjective day. Kinase ... FRQ recruits kinases such as casein kinase 1a (CK-1a) that phosphorylate WCC, although the function of these phosphorylations ... Additional interactions with other kinases including PRD-4 (CHK2) and casein kinase 2 (CKII) are known. Structural prediction ...
Stucke VM, Silljé HH, Arnaud L, Nigg EA (2002). "Human Mps1 kinase is required for the spindle assembly checkpoint but not for ... "Entrez Gene: TTK TTK protein kinase". Hanks SK, Quinn AM (1991). "Protein kinase catalytic domain sequence database: ... Dual specificity protein kinase TTK also known as Mps1 is an enzyme that in humans is encoded by the TTK gene. GRCh38: Ensembl ... 2003). "Human MPS1 Kinase Is Required for Mitotic Arrest Induced by the Loss of CENP-E from Kinetochores". Mol. Biol. Cell. 14 ...
In eukaryotes, the cellular repair response to DNA damage is orchestrated, in part, by the DNA damage checkpoint kinase ATM. ... Waterworth WM, Footitt S, Bray CM, Finch-Savage WE, West CE (2016). "DNA damage checkpoint kinase ATM regulates germination and ... Praha). 47 (2): 50-4. PMID 11321247. Waterworth WM, Masnavi G, Bhardwaj RM, Jiang Q, Bray CM, West CE (2010). "A plant DNA ... 169 (2): 914-930. doi:10.1104/pp.15.00498. ISSN 1532-2548. PMC 4587445. PMID 26276844. "A Sketch of an 8 Part Plant Hormone ...
... (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is ... Blasina A, de Weyer IV, Laus MC, Luyten WH, Parker AE, McGowan CH (Jan 1999). "A human homologue of the checkpoint kinase Cds1 ... The CHEK2 gene encodes for checkpoint kinase 2 (CHK2), a protein that acts a tumor suppressor. CHK2 regulates cell division, ... Cai Z, Chehab NH, Pavletich NP (Sep 2009). "Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase". ...
The DNA damage checkpoint kinase ATM has a major role in integrating progression through germination with repair responses to ... Waterworth WM, Footitt S, Bray CM, Finch-Savage WE, West CE (August 2016). "DNA damage checkpoint kinase ATM regulates ... Some seeds germinate when the soil is cool 28-40 F (-2 - 4 C), and some when the soil is warm 76-90 F (24-32 C). Some seeds ... 47 (2): 50-4. PMID 11321247. Waterworth WM, Masnavi G, Bhardwaj RM, Jiang Q, Bray CM, West CE (September 2010). "A plant DNA ...
"Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". The ... "Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 ... The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two ... A first group of protein kinases belongs to the MAPK family (JNK1-3, ERK1-2, p38 MAPK), which is known to respond to several ...
August 2007). "HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle ... Stage 2 (Moderate) Cannot work or maintain the more demanding aspects of daily life, but able to perform basic activities of ... 1 (2): 230-6. doi:10.1016/j.stem.2007.07.010. PMID 18371353. Thomas S, Mayer L, Sperber K (2009). "Mitochondria influence Fas ... 2 (6th ed.). Baltimore, MD: Williams and Wilkins. pp. 1644-1669. ISBN 978-0-683-04532-1.CS1 maint: multiple names: authors list ...
... (LY2606368) is a small molecule checkpoint kinase inhibitor, mainly active against CHEK1, with minor activity ... Al Idrus A (30 April 2019). "Lilly dumps phase 2 cancer drugs that survived previous cull". Fierce Biotech. "Clinical Trials ...
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. This ... Posas F, Saito H (1998). "Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator". ... Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ (1999). "Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E ... "p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase". Oncogene. 19 (40): ...
Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1)" (PDF). Journal of Medicinal Chemistry. ... November 2017). "Design of Leucine-Rich Repeat Kinase 2 (LRRK2) ... April 2018). "S55746 is a novel orally active BCL-2 selective ... 51 (2): 196-218. doi:10.1021/jm701018h. PMID 18020435. Jensen MR, Massey A, Schoepfer J, Brough PA (23 October 2013). ... August 2009). "Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[ ...
Yoshida K, Komatsu K, Wang HG, Kufe D (May 2002). "c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in ... "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... Agami R, Shaul Y (April 1998). "The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a ...
19] MPS1 is a protein kinase that is essential to the spindle assembly checkpoint, and it is thought to possibly remodel an ... Stucke VM, Silljé HH, Arnaud L, Nigg EA (April 2002). "Human Mps1 kinase is required for the spindle assembly checkpoint but ... "CDK2 cyclin dependent kinase 2 [Homo sapiens (human)]". Gene - NCBI. Retrieved 1 December 2019. Hinchcliffe EH, Li C, Thompson ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein ...
"Antitumor drug adozelesin differentially affects active and silent origins of DNA replication in yeast checkpoint kinase ... 275 (2): 1391-1397. doi:10.1074/jbc.275.2.1391. v t e. ...
Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. Two checkpoint kinase subtypes have been ... Goto H, Izawa I, Li P, Inagaki M (July 2012). "Novel regulation of checkpoint kinase 1: Is checkpoint kinase 1 a good candidate ... Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by ... Shieh SY, Ahn J, Tamai K, Taya Y, Prives C (February 2000). "The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) ...
"Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints ... Jin J, Ang XL, Ye X, Livingstone M, Harper JW (Jul 2008). "Differential roles for checkpoint kinases in DNA damage-dependent ... Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (Sep 1997). "Conservation of the Chk1 checkpoint ... Thus, this degradation represents one axis of a DNA damage checkpoint, complementing induction of p53 and p21 in the inhibition ...
The Tousled-like kinases, first described in Arabidopsis, are nuclear serine/threonine kinases that are potentially involved in ... and Chk1-dependent DNA damage checkpoint". The EMBO Journal. 22 (7): 1676-87. doi:10.1093/emboj/cdg151. PMC 152895. PMID ... Serine/threonine-protein kinase tousled-like 1 is an enzyme that in humans is encoded by the TLK1 gene. ... Groth A, Lukas J, Nigg EA, Silljé HH, Wernstedt C, Bartek J, Hansen K (Apr 2003). "Human Tousled like kinases are targeted by ...
"Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase". Nature. 411 (6833): 102-7. doi:10.1038/ ... Booher RN, Holman PS, Fattaey A (1997). "Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity ... CDC25B activates the cyclin dependent kinase CDC2 by removing two phosphate groups and it is required for entry into mitosis. ... CDC25B has been shown to interact with MAPK14, Casein kinase 2, alpha 1, CHEK1, MELK, Estrogen receptor alpha, YWHAB, YWHAZ, ...
The PLK4 inhibitor R1530 down regulates the expression of mitotic checkpoint kinase BubR1 that in turn leads to polyploidy ... Serine/threonine-protein kinase PLK4 also known as polo-like kinase 4 is an enzyme that in humans is encoded by the PLK4 gene. ... "Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase". The Journal of Biological Chemistry. 276 (42): 39012- ... Bailey AW, Suri A, Chou PM, Pundy T, Gadd S, Raimondi SL, Tomita T, Sredni ST (November 2018). "Polo-Like Kinase 4 (PLK4) Is ...
Lu R, Niida H, Nakanishi M (Jul 2004). "Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function". The ... "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1". The EMBO Journal. 23 (4): 833- ... BR serine/threonine kinase 1 is an enzyme that in humans is encoded by the BRSK1 gene. GRCh38: Ensembl release 89: ... Al-Hakim AK, Zagorska A, Chapman L, Deak M, Peggie M, Alessi DR (Apr 2008). "Control of AMPK-related kinases by USP9X and ...
An intra-S checkpoint also exists. Checkpoint activation is controlled by two master kinases, ATM and ATR. ATM responds to DNA ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating ... and some genes are involved in both DNA damage repair and cell cycle checkpoint control, for example ATM and checkpoint kinase ... Central to all DNA damage induced checkpoints responses is a pair of large protein kinases belonging to the first group of PI3K ...
Seemingly there are checkpoints for meiotic cell division too. In S. pombe, Rad proteins, S. pombe Mek1 (with FHA kinase domain ... doi.org/10.1101/cshperspect.a016634 Regulation of meiotic progression by the meiosis-specific checkpoint kinase Mek1 in fission ... Cdc25, Cdc2 and unknown factor is thought to form a checkpoint In vertebrate oogenesis, maintained by cytostatic factor (CSF) ... Checkpoints%20are%20regulatory%20mechanisms%20that,at%20the%20first%20meiotic%20division. Freeman, Scott (2005). Biological ...
... beta-secretase 1 and check point kinase 1 as case studies, Ma'mon M Hatmal et al. J Comput Aided Mol Des. 2016 Dec Hydrophobic ... to study the protein ligand interaction in cyclin-dependent kinase 5 and even to show the effect of electric field on thrombin ... "Steered Molecular Dynamics Simulations for Studying Protein-Ligand Interaction in Cyclin-Dependent Kinase 5". Journal of ... 241 (1-2): 51-58. doi:10.1016/j.fluid.2005.12.021. Justo, J. F.; Bazant, M. Z.; Kaxiras, E.; Bulatov, V. V.; Yip, S. (1998). " ...
"Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery". Current Biology. 16 (19): ... Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (Mar 2004). "M-phase kinases induce phospho- ... Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (Mar 2004). "M-phase kinases induce phospho- ... βTrCP plays important roles in regulating cell cycle checkpoints. In response to genotoxic stress, it contributes to turn off ...
Lin HR, Ting NS, Qin J, Lee WH (Sep 2003). "M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the ... Meiotic recombination checkpoint. *RecF pathway. *DNA helicase: BLM. *WRN. *FANC proteins: core protein complex *FANCA ... doi:10.1016/s1097-2765(00)80276-2. PMID 9774970.. *^ Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, ... Table 2. Altered expression of microRNAs that affect RAD51 expression in sporadic cancers. MicroRNA. miRNA Over/Under ...
The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". ... Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD (Jan 2005). "Sterile 20 kinase phosphorylates histone H2B at serine 10 ... SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ...
Interaction of human thymidine kinase 1 with p21(Waf1). „Biochem. J.". 356 (Pt 3), s. 829-34, 2001. PMID: 11389691. ... Identification of a functional domain in a GADD45-mediated G2/M checkpoint. „J. Biol. Chem.". 275 (47), s. 36892-8, 2000. DOI: ... Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ...
"Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint". Current Biology ... Karin M, Delhase M (February 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". ... Earlier cell cycle checkpoints such as post-restriction point check between G1 phase and S phase similarly involve proteasomal ... Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ...
The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... the PDGFs allow a cell to skip the G1 checkpoints in order to divide.[21] It has been shown that in monocytes-macrophages and ... The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... receptor tyrosine kinases". EMBO J. 15 (2): 290-298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.. ...
protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Early signaling steps implicate the following kinases and phosphatases after TCR triggering: *Lck - a Src family kinase ... Cancer immunotherapy and Checkpoint inhibition. ... This allows cytoplasmic kinases of the Syk family (ZAP-70) to ... FYN - a Src family kinase that phosphorylates CD3 and ζ ITAMs. *CD45 - a transmembrane protein whose intracellular tail ... Zap70 - a Syk family kinase that binds to ITAM sequences upon tyrosine phosphorylation by Lck and Fyn, and phosphorylates LAT ...
Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S (August 2001). "PRMT5 (Janus kinase-binding protein 1) ... "The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair ... 2][3][4] In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.[ ...
"A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade". Cell. 175 (4): 984-997.e24. doi ... the depth of complexity and compound mutations present in amplified therapeutic targets such as receptor tyrosine kinase genes ... 176 (1-2): 98-112.e14. doi:10.1016/j.cell.2018.11.046. PMC 6363966. PMID 30633912.. ... A typical human cell consists of about 2 x 3.3 billion base pairs of DNA and 600 million bases of mRNA. Usually a mix of ...
... checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.[185] ... stimulates the focal adhesion kinase (FAK) signaling pathway which leads to prostate cancer cell growth and survival.[65] ... 53 (2): 171-84. doi:10.1002/mnfr.200700511. PMID 19101947.. *^ a b Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT (September ... 2 (5): 389-96. doi:10.1038/nrc801. PMC 4124639 . PMID 12044015.. *^ Scott WW, Johnson DE, Schmidt JE, Gibbons RP, Prout GR, ...
kinase binding. • mitogen-activated protein kinase kinase binding. • guanylate kinase activity. • protein binding. • protein ... mitotic cell cycle checkpoint. • receptor clustering. • positive regulation of establishment of protein localization to plasma ... protein kinase binding. • L27 domain binding. • ligand-gated ion channel activity. • potassium channel regulator activity. • ... activation of protein kinase activity. • negative regulation of mitotic cell cycle. • regulation of membrane potential. • ...
cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine kinase activity. • ... "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". J. Biol. Chem. 275 (47): 36892-8. doi:10.1074/jbc. ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ...
Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... The phases follow one another in strict order and there are "checkpoints" that give the cell cues to proceed from one phase to ... Zhou J, Yao J, Joshi HC (September 2002). "Attachment and tension in the spindle assembly checkpoint". Journal of Cell Science ... Kops GJ, Weaver BA, Cleveland DW (October 2005). "On the road to cancer: aneuploidy and the mitotic checkpoint". Nature Reviews ...
PARP1 is over-expressed in tyrosine kinase-activated leukemias,[28] in neuroblastoma,[29] in testicular and other germ cell ... XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory ... 2. /. length of sequence. {\displaystyle (({\text{number of }}C+{\text{number of }}G)/2)^{2}/{\text{length of sequence}}}. [7] ... doi:10.1007/978-3-319-42059-2_6. PMID 27573897.. *^ a b Bird A (2002). "DNA methylation patterns and epigenetic memory". Genes ...
Approaches include antibodies, checkpoint therapy and adoptive cell transfer.[161] Laser therapy. Main article: Lasers in ... an oncogenic tyrosine kinase. ... 2 Signs and symptoms *2.1 Local symptoms. *2.2 Systemic ... 61 (2): 69-90. doi:10.3322/caac.20107. PMID 21296855.. *^ World Cancer Report 2014. World Health Organization. 2014. pp. ... 21 (2): 196-227. PMC 1706430. PMID 5770175.. *^ O'Hagan HM, Mohammad HP, Baylin SB (August 2008). Lee JT, ed. "Double strand ...
"WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Letters. 575 (1-3 ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... 2 (2): 84-9. doi:10.1038/35000034. PMID 10655587.. *^ a b Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio ... 2 (2): 76-83. doi:10.1038/35000025. PMID 10655586.. *^ a b Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Cell cycle checkpoints. *Restriction point. *Spindle checkpoint. *Postreplication checkpoint. Other cellular phases. *Apoptosis ... doi: /10.1007/s10565-019-09496-2. PMID 31820165 *^ a b c d e f g Cotran RS, Kumar C (1998). Robbins Pathologic Basis of Disease ... Bcl-2 family. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. ...
mitogen-activated protein kinase kinase kinase binding. • protein binding. • thioesterase binding. • protein kinase binding. • ... "The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily ... Cell cycle checkpoints. *Restriction point. *Spindle checkpoint. *Postreplication checkpoint. Other cellular phases. *Apoptosis ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
LAG-3 may be a better checkpoint inhibitor target than CTLA-4 or PD-1 since antibodies to these two checkpoints only activate ... "Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling". Journal ... It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies ... LAG-3: Identification & Validation Of Next Generation Checkpoint Pathway by Frédéric Triebel March 22, 2018 ...
Erlotinib, gefitinib and afatinib inhibit tyrosine kinase at the epidermal growth factor receptor. Denosumab is a monoclonal ... Many of these new treatments work through immune checkpoint blockade, disrupting cancer's ability to evade the immune system.[ ... For lung cancer cases that develop resistance to epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) ... 2): S6-S13. doi:10.1038/bjc.2011.475. PMC 3252064 . PMID 22158323.. *^ a b Taylor, R; Najafi F; Dobson A (October 2007). "Meta- ...
有些肺癌患者已对表皮生长因子受体(EGFR)和间变性淋巴瘤激酶(英语:anaplastic lymphoma kinase)(ALK)的酪氨酸激酶抑制剂(英语:Kinase tyrosine-based inhibitory motif)產生耐受性,故有 ... 当前肺癌治疗的研究方向包括免疫治疗(激活机体免疫系统攻击肿瘤细
"Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress". Genes Dev. 14 (23): 2989-3002. ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... ATM/ATR are kinases activated by DNA damage. Mutation of serine residues may affect localization of BRCA1 to sites of DNA ...
"DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds". PNAS. 113 (34): 9647-9652. doi ... 2. +. 6. H. 2. O. →. light. C. 6. H. 12. O. 6. +. 6. O. 2. {\displaystyle {\ce {6CO2{}+6H2O{}-,[{\text{light}}]C6H12O6{}+6O2 ... The DNA checkpoint kinase ATM has a key role in integrating progression through germination with repair responses to the DNA ... 2000). "FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis". ...
CDK抑制因子(英语:Cyclin-dependent kinase inhibitor protein). *INK4a/ARF(p14arf/p16、p15、p18、p19) ... 细胞生长停止在这个阶段,细胞能量集中在有序地分裂成两个子细胞。有丝分裂中期的检查点(Metaphase Checkpoint)确保细胞可以完成细胞分裂。 ... 細胞週期的劃分:G1期→S期→G2期→M期,以及G0期。. G1期:進行細胞生長,S
Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins ... Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in ... For example, disruption of the interaction between InaC, the protein kinase C, and InaD results in a delay in inactivation of ... 2: e00231. doi:10.7554/eLife.00231. PMC 3545443. PMID 23326642.. *^ a b c Szczecinski NS, Bockemühl T, Chockley AS, Büschges A ...
Phosphorylation by cAMP-dependent protein kinasesEdit. Cyclic AMP-dependent protein kinases (protein kinase A) are activated by ... Margeta-Mitrovic M, Jan YN, Jan LY (July 2000). "A trafficking checkpoint controls GABA(B) receptor heterodimerization". Neuron ... The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs.[53] G-protein-coupled ... these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and ...
"DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds". Proc. Natl. Acad. Sci. U.S.A. ... The DNA checkpoint kinase ATM has a key role in integrating progression through germination with repair responses to the DNA ... 2000). "FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis". ... 84 (2): 149-165. doi:10.5586/asbp.2015.020.. *^ a b Sánchez-Baracaldo, Patricia; Raven, John A.; Pisani, Davide; Knoll, Andrew ...
For his discovery of components and regulators of the mTOR kinase pathway and his elucidation of the important roles of this ... For his innovative contributions at the forefront of the field of cell cycle checkpoints and his elucidation of pathways and ... For his creative use of elegant biochemistry both in elucidating an unsuspected role for polyubiquitin in a kinase-signaling ... Retrieved 2 August 2018.. *^ "Sue Biggins receives the National Academy of Sciences Award in Molecular Biology". The Raymond ...
"WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Lett. 575 (1-3): 23 ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". J. Cell Biol. 128 (5): 949-57. PMC ... 14,0 14,1 14,2 14,3 Kinch MS, Clark GJ, Der CJ, Burridge K (July 1995). "Tyrosine phosphorylation regulates the adhesions of ... 17,0 17,1 17,2 Piedra J, Miravet S, Castaño J, Pálmer HG, Heisterkamp N, García de Herreros A, Duñach M (April 2003). "p120 ...
de 2003). «Modulation of human checkpoint kinase Chk1 by the regulatory beta-subunit of protein kinase CK2». Oncogene (England ... de 2004). «Phosphorylation of the regulatory beta-subunit of protein kinase CK2 by checkpoint kinase Chk1: identification of ... de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ... de 2003). «Protein kinase CK2 regulates CDC25B phosphatase activity». Oncogene (England) 22 (2): 220-32. ISSN 0950-9232. PMID ...
Previous Names: "CHK2 (checkpoint, S.pombe) homolog", "CHK2 checkpoint homolog (S. pombe)" ...
Crystal Structure of Checkpoint Kinase 2 in Complex with Nsc 109555, a Potent and Selective Inhibitor.. Lountos, G.T.,& ... Structural analysis of checkpoint kinase 2 in complex with inhibitor PV1322. *DOI: 10.2210/pdb2YIQ/pdb ... The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule ... The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule ...
Activated Checkpoint Kinase 2 Expression and Risk for Oral Squamous Cell Carcinoma. Angela J. Yoon, Jing Shen, Regina M. ... Background: Phosphoactivation of a DNA damage response molecule checkpoint kinase 2 (pChk2) may be a marker of oral epithelial ... During the normal cellular response to DNA damage, the checkpoint kinase 2 (Chk2) protein is phosphorylated at threonine ... Activated Checkpoint Kinase 2 Expression and Risk for Oral Squamous Cell Carcinoma ...
The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles ... The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles ... The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles ... The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles ...
Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor ... Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor ... Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor ... Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor ...
Checkpoint kinase 2 and androgen receptor cross-talk regulate the DDR and prostate cancer growth. Huy Q Ta, Rosalie Sleppy, ... Checkpoint kinase 2 (CHK2) is a serine/threonine protein kinase whose main function is regulating the DNA damage response (DDR ... Checkpoint kinase 2 and androgen receptor cross-talk regulate the DDR and prostate cancer growth (. ... The binding of CHK2 with AR can be disrupted with CHK2 kinase inhibitors suggesting that the kinase activity of CHK2 is ...
Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium ... Herpes simplex virus type 1 Keratitis Checkpoint kinase 2 Corneal epithelium Explant cornea DNA damage response Small-molecule ... This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. ,b ... Supplementary Material for: Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in ...
The compound also targets Aurora A kinase and tubulin in vitro and in cells, which can explain the observed spindle anomalies. ... The reduced activity of Aurora B kinase resulted in polyploidy and suppression of cancer cell viability. Our data suggest that ... One potential drug target within the mitotic machinery is the spindle assembly checkpoint (SAC), an evolutionarily conserved ... One potential drug target within the mitotic machinery is the spindle assembly checkpoint (SAC), an evolutionarily conserved ...
Central to this network are protein kinases of the PIKK (phosphoinositide 3-kinase-related protein kinase) family, like ATM ( ... 1996 rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science 271: 353-356. ... Activation of Checkpoint Kinase Chk1 by Reactive Oxygen Species Resulting from Disruption of wat1/pop3 in Schizosaccharomyces ... Activation of Checkpoint Kinase Chk1 by Reactive Oxygen Species Resulting from Disruption of wat1/pop3 in Schizosaccharomyces ...
Category: Checkpoint Kinase Published November 4, 2018 Background/Purpose Transforming growth issue triggered kinase 1 (TAK1) ... Background/Purpose Transforming growth issue triggered kinase 1 (TAK1) is usually an integral MAPKKK family protein in ... Continue reading Background/Purpose Transforming growth issue triggered kinase 1 (TAK1) is usually an ... Changed expression of Bcl-2 family proteins performs central roles in apoptosis dysregulation in cancer and leukemia, promoting ...
In mammalian cells, four protein kinases form the PI3-kinase-related protein kinase (PIK) superfamily. These four enzymes-FRAP ... and their sequence similarity to the p110 lipid kinase subunit of PI3-kinase. FRAP (FKBP12 and rapamycin-binding protein kinase ... Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family.. Hoekstra MF1. ... Recent studies in this protein kinase family indicate an important role for ATM and ATR in a meiotic surveillance mechanism ...
Mitotic kinases as regulators of cell division and its checkpoints.. Nigg EA1. ... Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission. ...
The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will ... The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In ... The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In ... The meiotic roles of the canonical checkpoint kinases Bub1, Mps1... ...
Mitotic checkpoint serine/threonine-protein kinase BUB1Imported. ,p>Information which has been imported from another database ... tr,C9JQA4,C9JQA4_HUMAN Mitotic checkpoint serine/threonine-protein kinase BUB1 (Fragment) OS=Homo sapiens GN=BUB1 PE=1 SV=1 ... 2 - 146. BUB1 N-terminalInterPro annotation. ,p>Information which has been generated by the UniProtKB automatic annotation ...
DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2. By Atsushi Hirao, Young-Yun Kong, Shuhei Matsuoka, Andrew ... DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2. By Atsushi Hirao, Young-Yun Kong, Shuhei Matsuoka, Andrew ... DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2 Message Subject. (Your Name) has forwarded a page to you ... E) Kinase activity of Cdc2 in Chk2+/+ and Chk2−/− ES cells at the indicated times after 10 Gy of γ irradiation. In vitro kinase ...
Defects in the IR-induced S-phase checkpoint cause radioresistant DNA synthesis, a phenomenon that has been identified in ... eukaryotic cells activate checkpoint pathways to delay the progression of the cell cycle. ... Here we report a functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A, and implicate this ... The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis Nature. 2001 Apr 12;410(6830):842-7. doi: ...
Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase. Seiji Matsumoto, Yutaka Kanoh ... Checkpoint-independent regulation of origin firing by Mrc1 through interaction with Hsk1 kinase. Mol Cell Biol 37:e00355-16. ... Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase ... Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase ...
Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. We ... AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer ... Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther ... as well as one mitotic spindle checkpoint (1). Checkpoint kinase 1 (Chk1) is a key regulator of S, G2-M, and mitotic spindle ...
Mechanisms of Checkpoint Kinase Rad53 Inactivation after a Double-Strand Break in Saccharomyces cerevisiae. Ghislaine ... Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol. Cell7:293-300. ... Mechanisms of Checkpoint Kinase Rad53 Inactivation after a Double-Strand Break in Saccharomyces cerevisiae ... Mechanisms of Checkpoint Kinase Rad53 Inactivation after a Double-Strand Break in Saccharomyces cerevisiae ...
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature. 455:119-123. doi:10.1038/nature07185. ... Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing. Dan Liu, Olga Davydenko, ... Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing ... Polo-like kinase-1 (Plk1) is a highly conserved kinase with multiple mitotic functions. Plk1 localizes to prometaphase ...
The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells. ... The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells ... The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells ... The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells ...
... kinase (MEK) can induce regression of tumors bearing activating mutations in the Ras pathway but rarely leads to tumor ... Targeted inhibition of mitogen-activated protein kinase (MAPK) ... MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity ... Targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) can induce regression of tumors bearing activating ... Epub 2016 Mar 2. Authors Peter J R Ebert 1 , Jeanne Cheung 1 , Yagai Yang 1 , Erin McNamara 1 , Rebecca Hong 1 , Marina ...
... Breast cancer. Prostate cancer. Li-Fraumeni /Li-Fraumeni-like Syndrome. ... CHEK2 encodes a Serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways1. CHEK2 directly ... phosphorylates and regulates the functions of p53 and BRCA1 2,3. Most women with breast and/or ovarian cancer are not carriers ...
... a small-molecule inhibitor of checkpoint kinase 1 (Chk1) ... ProNAi Licenses Checkpoint Kinase 1 Inhibitor from CRT Pioneer ... Home Topics Cancer ProNAi Licenses Checkpoint Kinase 1 Inhibitor from CRT Pioneer Fund ... a small-molecule inhibitor of checkpoint kinase 1 (Chk1). ... 2 .entry-title { font-size: 17px; line-height: 20px; }. ...
Chk2 (Checkpoint kinase 2) is considered a tumor suppressor gene that acts on the cellular response to DNA damage. However, the ... Immunohistochemistry analysis of checkpoint kinase 2 in oral squamous cell carcinoma. Access & Citations. * 957 Article ...
Expression of Oncogenic Kinase Bcr-Abl Impairs Mitotic Checkpoint and Promotes Aberrant Divisions and Resistance to Microtubule ... Expression of Oncogenic Kinase Bcr-Abl Impairs Mitotic Checkpoint and Promotes Aberrant Divisions and Resistance to Microtubule ... Expression of Oncogenic Kinase Bcr-Abl Impairs Mitotic Checkpoint and Promotes Aberrant Divisions and Resistance to Microtubule ... Expression of Oncogenic Kinase Bcr-Abl Impairs Mitotic Checkpoint and Promotes Aberrant Divisions and Resistance to Microtubule ...
... checkpoint through inhibition of Plk1 kinase. Together they form a unique fingerprint. * Sort by ... Fingerprint Dive into the research topics of ATR enforces the topoisomerase II-dependent G(2) ... ATR enforces the topoisomerase II-dependent G(2) checkpoint through inhibition of Plk1 kinase. ...
Abbreviations: CHEK2, checkpoint kinase 2; SCD: N-terminal SQ/TQ cluster domain; FHA, forkhead-associated domain; NR: not ... When double-stranded DNA is damaged, checkpoint kinase 2 (CHEK2) is phosphorylated, which in turn phosphorylates its downstream ... When double-stranded DNA is damaged, checkpoint kinase 2 (CHEK2) is phosphorylated, which in turn phosphorylates its downstream ... Y390C mutation occurs in the serine/threonine kinase domain,[26] which disrupts the kinase function of CHEK2 and prevents the ...
Checkpoint Kinase 1. Synthetic lethality. Next-Generation Sequencing. Genetic biomarkers. Additional relevant MeSH terms:. ... Recommended Phase 2 dose of SRA737 in combination with gemcitabine. [ Time Frame: Up to 30 days after last dose of SRA737 ]. ... A Phase 1/2 Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Alone ... A Phase 1/2 Trial of SRA737 in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Alone in Subjects With Advanced ...
Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. ... Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors ... Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors ... Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors ...
  • The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer. (rcsb.org)
  • X-ray crystallography was used to determine the structures of the inhibitors in complex with the catalytic kinase domain of Chk2 to verify their modes of binding. (rcsb.org)
  • During the normal cellular response to DNA damage, the checkpoint kinase 2 (Chk2) protein is phosphorylated at threonine residue 68 to generate an enzymatically active isoform of the protein, hereafter called pChk2. (aacrjournals.org)
  • Checkpoint kinase 2 (CHK2) is a serine/threonine protein kinase whose main function is regulating the DNA damage response (DDR) triggered by double-strand DNA breaks. (endocrine-abstracts.org)
  • The binding of CHK2 with AR can be disrupted with CHK2 kinase inhibitors suggesting that the kinase activity of CHK2 is required. (endocrine-abstracts.org)
  • This was verified using kinase impaired CHK2 variants, including the K373E variant associated with 4.2% of prostate cancer. (endocrine-abstracts.org)
  • This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. (figshare.com)
  • Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. (figshare.com)
  • This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. (figshare.com)
  • Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. (sciencemag.org)
  • Chk2 −/− embryonic stem cells failed to maintain γ-irradiation-induced arrest in the G 2 phase of the cell cycle. (sciencemag.org)
  • Chk2 is a mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 checkpoint genes. (sciencemag.org)
  • Chk2 is a protein kinase that acts downstream of ataxia teleangiecstasia mutated (ATM) and may regulate cell cycle arrest ( 2-4 ). (sciencemag.org)
  • Because Chk2 is thought to have a role in the prevention of entry into mitosis ( 2-4 ), we examined arrest of the cell cycle in ES cells, a cell type in which γ irradiation induces arrest in the G 2 phase but not arrest in the G 1 phase or apoptosis ( 7 ). (sciencemag.org)
  • Twelve hours after 10 grays (Gy) of γ irradiation, about 90% of both Chk2 +/+ and Chk2 −/− ES cells were arrested with a G 2 DNA content ( Fig. 1 C). However, at later time points, substantially more Chk2 −/− cells entered G 1 and S relative to controls. (sciencemag.org)
  • In the absence of γ irradiation, about 35% of cells of both genotypes were trapped in mitosis after 12 hours of nocodazole treatment ( Fig. 1 D). When cells were subjected to γ irradiation with nocodazole treatment, cells of both genotypes arrested in G 2 for 12 hours ( Fig. 1 D). However, after 18 hours, significantly more Chk2 −/− cells entered mitosis. (sciencemag.org)
  • p53 −/− ES cells did not show a defect in cell cycle arrest after γ irradiation ( Fig. 1 C), as previously shown ( 7 ), indicating that the defect in G 2 arrest observed in Chk2 −/− ES cells is p53-independent. (sciencemag.org)
  • Failure of maintenance of γ irradiation-induced G 2 arrest in Chk2 −/− ES cells. (sciencemag.org)
  • Here we report a functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A, and implicate this mechanism in controlling the S-phase checkpoint. (nih.gov)
  • These results support Chk2 as a candidate tumour suppressor, and identify the ATM-Chk2-Cdc25A-Cdk2 pathway as a genomic integrity checkpoint that prevents radioresistant DNA synthesis. (nih.gov)
  • Rad53 is the founding member of the conserved family of FHA (forkhead associated) domain-containing checkpoint kinases, which also includes mammalian Chk2 and Schizosaccharomyces pombe Cds1. (asm.org)
  • DDR is mediated by a signal transduction cascade involving the ataxia telangiectasia mutated (ATM-) check point kinase 2 (Chk2)-p53 axis [ 8 , 9 ]. (hindawi.com)
  • Checkpoint kinase 2 (CHK2) is a DNA damage -activated protein kinase which is involved in cell cycle checkpoint control . (bvsalud.org)
  • Analysis of proteins that regulate cell cycle arrest suggested that both drugs inhibit the checkpoint kinases Chk1 and/or Chk2. (aacrjournals.org)
  • The checkpoint kinase CHK2 is the mammalian homologue of yeast Cds1/Rad53. (acris-antibodies.com)
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates CHK2, which in turn directly phosphorylates and activates p53. (acris-antibodies.com)
  • one of these genes is CHEK2 , a tumor suppressor gene that encodes a serine/threonine kinase, the CHK2. (dovepress.com)
  • PDE5 inhibitors enhanced and prolonged the induction of DNA damage as judged by Comet assays and γ histone 2AX ( γ H2AX) and checkpoint kinase 2 (CHK2) phosphorylation. (aspetjournals.org)
  • p-H2AX Ser 139 mAb (2577S), p-p53 Ser15 mAb (9284S), p-Chk2 Thr68 mAb (2661) Anti-rabbit IgG HRP linked (7074), Anti-mouse IgG HRP linked secondary antibody (7076), Anti-IgG (H+L) F(ab′)2 Alexa Fluor 488 (4412) and Anti-rabbit IgG (H+L) F(ab′)2 Alexa Fluor 555 (Cat. (biomedcentral.com)
  • Previously, it was reported that two kinases essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. (biologists.org)
  • CHEK2 encodes a Serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways 1 . (cityofhope.org)
  • CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1 2,3 . (cityofhope.org)
  • CHEK2 has 3 functional domains, namely, N-terminal SQ/TQ cluster domain (SCD), central forkhead-associated (FHA) domain, and C-terminal serine/threonine-kinase domain (KD), each of which has specific functions. (medscape.com)
  • Y390C mutation occurs in the serine/threonine kinase domain, [ 26 ] which disrupts the kinase function of CHEK2 and prevents the phosphorylation of downstream factors in the signaling pathway. (medscape.com)
  • When double-stranded DNA is damaged, checkpoint kinase 2 ( CHEK2 ) is phosphorylated, which in turn phosphorylates its downstream factors, such as P53, P21, the breast cancer gene ( BRCA ), and cell division cycle 25A (CDC25A). (medscape.com)
  • Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. (cdc.gov)
  • Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. (plos.org)
  • Checkpoint kinase 2 (CHEK2) is a serine/threonine kinase which is activated upon DNA damage and is implicated in pathways that govern DNA repair, cell cycle arrest or apoptosis in response to the initial damage. (dovepress.com)
  • CHEK2 gene is activated by phosphorylation of Thr68 by ATM , which causes the dimerization of the gene enabling it to acquire kinase activity. (dovepress.com)
  • CHEK2 then reacts with downstream phosphatase CDC25, serine/threonine protein kinase NEK6, transcription factor FOXM1, p53 protein and BRCA1 or BRCA2. (dovepress.com)
  • Partial sequences of exon 10 and exon 2 of CHEK2. (nih.gov)
  • Multiple checkpoint kinase 1 (Chk1) inhibitors have been actively pursued in clinical trials for their ability to sensitize the efficacy of DNA-damaging agents or radiation. (aacrjournals.org)
  • The critical involvement of Chk1 in the spindle checkpoint also suggests that Chk1 inhibitors may be used to potentiate taxane therapy. (aacrjournals.org)
  • The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
  • Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. (springer.com)
  • Because UCN-01 also inhibits protein kinase C (PKC), we screened other PKC inhibitors, expecting them to be unable to abrogate arrest. (aacrjournals.org)
  • Considering the difficulties with UCN-01, we have sought checkpoint inhibitors that abrogate damage-induced arrest but lack these undesirable additional properties ( i.e. , plasma binding and nonspecific kinase inhibition). (aacrjournals.org)
  • KU0058684 and KU0058948 are potent and specific inhibitors of PARP-1 and PARP-2 but not of vault PARP or tankyrase PARP ( 8 ). (aacrjournals.org)
  • New side-effects observed in melanoma patients receiving immune checkpoint and/or kinase inhibitors are a matter of concern. (lww.com)
  • Melanoma Research has published many new findings and there has been a continuous increase in the number of reports relating to immunotherapy and kinase inhibitors. (lww.com)
  • Mitotic cells were collected and lysed in 50 mM Tris (pH 7.5), 200 mM NaCl, 1% Triton X-100, 1.5 mM MgCl 2 , and 5 mM EDTA, supplemented with protease and phosphatase inhibitors. (pnas.org)
  • Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes. (jimmunol.org)
  • To discover more about the functions of Aurora A, Aurora B, and kinases of the Plk family, we mapped mitotic phosphorylation sites to these kinases through the combined use of quantitative phosphoproteomics and selective targeting of kinase activities by small-molecule inhibitors. (sciencemag.org)
  • Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI). (dana-farber.org)
  • We conclude that Mps1 has two complementary roles in SAC regulation: (1) initial cytoplasmic activation of Cdc20 inhibitors and (2) recruitment of factors that promote sustained anaphase inhibition and chromosome biorientation to unattached kinetochores. (pubmedcentralcanada.ca)
  • We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. (springer.com)
  • Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising new treatment in various cancer types. (springer.com)
  • Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. (springer.com)
  • Thetext also describes existing and emerging kinase inhibitors,focusing mostly on small molecules but also alternative approacheslike therapeutic antibodies. (whsmith.co.uk)
  • Our data thus strongly suggest that CK2 is the kinase responsible for the in vivo phosphorylation of Ptc2 T376. (asm.org)
  • Once activated, Mec1 induces the phosphorylation and the activation of two central transducers, the Rad53 and Chk1 kinases, which subsequently phosphorylate downstream effectors. (asm.org)
  • Phosphorylation of CDC25C by CHK 1 and 2 inhibits its phosphatase activity, thereby blocking mitosis. (acris-antibodies.com)
  • Aurora B kinase activity is also required for phosphorylation of BubR1 on entry into mitosis. (rupress.org)
  • As FRQ is produced, it dimerizes and interacts with FRQ Interacting RNA Helicase (FRH) and casein kinase 1 (CK1), leading to the inhibition of WCC and correlated with phosphorylation events that involve several kinases, including CK1, thereby closing the TTFL. (genetics.org)
  • Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. (nature.com)
  • Protein phosphorylation by a small number of kinases, in particular Aurora A, Aurora B, the cyclin-dependent kinase-cyclin complex Cdk1/cyclinB, and Polo-like kinase 1 (Plk1), orchestrates almost every step of cell division, from entry into mitosis to cytokinesis. (sciencemag.org)
  • Although these processes are diverse and executed by a cadre of functional classes of proteins, posttranslational protein phosphorylation by a small group of serine-threonine kinases orchestrates many aspects of most steps from mitotic entry to exit. (sciencemag.org)
  • In addition, the crucial checkpoint protein Rad53 acted as an upstream regulator of Rph1 and dominated the phosphorylation of Rph1 that was required for efficient PHR1 expression and the dissociation of Rph1. (nih.gov)
  • By autoradiography, we detected a specific signal of Rph1 phosphorylation in the presence of WT Rad53 but not rad53-KD, which established that Rad53 kinase dominated the phosphorylation of Rph1 (Figure 6A). (nih.gov)
  • abolishes Cdc2 phosphorylation in numerous tumor cell lines and abrogates the G 2 checkpoint. (rndsystems.com)
  • Espert A, Uluocak P, Bastos RN, Mangat D, Graab P, Gruneberg U. PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing. (springer.com)
  • Jia L, Li B, Yu H. The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. (springer.com)
  • Although ATM phosphorylated Ser-101 but not Ser-56 on Sp1 in vitro, phosphorylation of Sp1 at both sites was not detected at all upon infection in ATM-deficient cells, suggesting that cellular kinase(s) activated by ATM could be involved in phosphorylation at Ser-56. (asm.org)
  • It has been recently demonstrated that phosphorylation of Sp1 alters its transcription activity in a wide variety of physiological processes, including cell cycle progression, terminal differentiation, and viral infection ( 2 , 9 , 17 , 23 , 28 , 36 , 41 ). (asm.org)
  • Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. (aacrjournals.org)
  • Docetaxel triggers mitotic spindle checkpoint activation at low concentrations and activates both the DNA damage checkpoint and the spindle checkpoint at high concentrations. (aacrjournals.org)
  • Docetaxel treatment leads to the dose- and time-dependent activation of the DNA damage checkpoint, as well as the mitotic spindle checkpoint. (aacrjournals.org)
  • There are at least three DNA damage checkpoints, at the G 1 -S, S, and G 2 -M transitions, as well as one mitotic spindle checkpoint ( 1 ). (aacrjournals.org)
  • Plk1 localizes to prometaphase kinetochores and is reduced at metaphase kinetochores, similar to many checkpoint signaling proteins, but Plk1 is not required for spindle checkpoint function. (rupress.org)
  • Together, our data show that Plk1 dynamics at kinetochores control two critical mitotic processes: initially establishing correct kinetochore-microtubule attachments and subsequently silencing the spindle checkpoint. (rupress.org)
  • Because Plk1 reduction at kinetochores is puzzling in the context of regulating microtubule attachments and is apparently not an integral component of the spindle checkpoint, Plk1 function at kinetochores is unclear. (rupress.org)
  • Despite the presence of maloriented chromosomes, ZM447439-treated cells exit mitosis with normal kinetics, indicating that the spindle checkpoint is compromised. (rupress.org)
  • In the absence of Aurora B function, kinetochore localization of the spindle checkpoint components BubR1, Mad2, and Cenp-E is diminished. (rupress.org)
  • Finally, we show that BubR1 is not only required for spindle checkpoint function, but is also required for chromosome alignment. (rupress.org)
  • Although it is well established that a surveillance mechanism, the spindle checkpoint, delays anaphase until all chromosomes correctly bi-orient (for review see Musacchio and Hardwick, 2002 ), the mechanisms that detect and resolve orientation errors are poorly understood. (rupress.org)
  • Because kinetochores in these cells lack sisters, they fail to come under tension despite microtubule attachment, arguing that Ipl1 is required for spindle checkpoint activation in response to loss of tension at centromeres. (rupress.org)
  • We have been studying genes that regulated the spindle checkpoint in human cells. (semanticscholar.org)
  • See " Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine " in volume 190 on page 73. (pubmedcentralcanada.ca)
  • Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis. (springer.com)
  • Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C. Characterization of MAD2B and other mitotic spindle checkpoint genes. (springer.com)
  • Elowe S. Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. (springer.com)
  • Encalada SE, Willis J, Lyczak R, Bowerman B. A spindle checkpoint functions during mitosis in the early Caenorhabditis elegans embryo. (springer.com)
  • Espeut J, Lara-Gonzalez P, Sassine M, Shiau AK, Desai A, Abrieu A. Natural loss of Mps1 kinase in nematodes uncovers a role for polo-like kinase 1 in spindle checkpoint initiation. (springer.com)
  • Structure and substrate recruitment of the human spindle checkpoint kinase Bub1. (springer.com)
  • HEC is one of several proteins involved in spindle checkpoint signaling. (wikipedia.org)
  • One potential drug target within the mitotic machinery is the spindle assembly checkpoint (SAC), an evolutionarily conserved signaling pathway that monitors the connections between microtubules (MTs) and chromosomes. (oup.com)
  • In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. (frontiersin.org)
  • We report that CK2 is essential for porcine oocyte meiotic maturation by regulating spindle assembly checkpoint (SAC). (biomedcentral.com)
  • Apart from its well-known role in DNA repair, BRCA1 acts also as a factor-regulating gene expression for orderly mitotic progression, namely those involved in the spindle assembly checkpoint (SAC), also called the mitotic checkpoint ( 8 , 9 ). (aacrjournals.org)
  • The RZZ complex and the spindle assembly checkpoint. (semanticscholar.org)
  • It has recently been reported that microtubule depolymerization by nocodazole treatment can block exit from mitosis in the extracts if enough sperm nuclei are present, and that the addition of MAP kinase- specific phosphatase MKP-1 overcomes this spindle assembly checkpoint, suggesting the involvement of MAP kinase in the checkpoint signal transduction. (rupress.org)
  • We show here that the spindle assembly checkpoint mechanism cannot operate in the MAP kinase-depleted extracts. (rupress.org)
  • But, adding recombinant Xenopus MAP kinase to the MAP kinase-depleted extracts restored the spindle assembly checkpoint. (rupress.org)
  • These results indicate unambiguously that classical MAP kinase is required for the spindle assembly checkpoint in the cell cycle extracts. (rupress.org)
  • 20 ) has identified MAP kinase or a related molecule(s) as a component of the embryonic spindle assembly checkpoint in Xenopus egg cell cycle extracts. (rupress.org)
  • The spindle assembly checkpoint (SAC) in mammals uses cytosolic and kinetochore-based signaling pathways to inhibit anaphase. (pubmedcentralcanada.ca)
  • Paramount among these is the so-called spindle assembly checkpoint (SAC), which inhibits anaphase onset until all kinetochore pairs have attached to microtubules (MTs) emanating from both spindle poles, generating a stable configuration termed chromosome biorientation (for review see Musacchio and Salmon, 2007 ). (pubmedcentralcanada.ca)
  • Through its capacity to contribute to mitotic arrest, BUB1 functions as an integral component of the spindle assembly checkpoint (SAC), a surveillance mechanism that delays mitotic progression until all kinetochores are properly attached to microtubules, and aligned at the spindle equator in metaphase. (springer.com)
  • Bokros M, Gravenmier C, Jin F, Richmond D, Wang Y. Fin1-PP1 helps clear spindle assembly checkpoint protein Bub1 from kinetochores in anaphase. (springer.com)
  • Finally, aurora B-null cells partially arrest in the presence of nocodazole, suggesting that this kinase is not essential for the spindle assembly checkpoint. (biologists.org)
  • Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. (biochemsoctrans.org)
  • UCN-01 did not demonstrate this selectivity for checkpoint inhibition. (aacrjournals.org)
  • Inhibition of damage-induced checkpoints by pharmacological means leads to abrogation of cell cycle arrest and subsequent lethal mitosis, thereby sensitizing cells to DNA-damaging agents. (aacrjournals.org)
  • Considering that Chk1/2 kinases exert an essential role in the control of cell cycle, inhibition of Chk1/2 by QNC may induce cell death via uncontrolled cell cycle progression. (aacrjournals.org)
  • RNA interference experiments suggest that these phenotypes are due to inhibition of Aurora B, not Aurora A or some other kinase. (rupress.org)
  • Furthermore, inhibition of Aurora B kinase activity prevents the rebinding of BubR1 to metaphase kinetochores after a reduction in centromeric tension. (rupress.org)
  • To determine the short- and long-term effects of mitotic checkpoint inhibition on survival of individual cells, the critical checkpoint proteins BubR1 or Mad2 were reduced by plasmid-based expression of double-stranded small interfering RNAs (siRNAs) ( 15 ). (pnas.org)
  • Guided by homology modeling of the Plk1 kinase domain, we have discovered a chemical series that shows potent and selective Plk1 inhibition. (nature.com)
  • 1.5.2 Alternative Strategies for Kinase Inhibition. (whsmith.co.uk)
  • Changed expression of Bcl-2 family proteins performs central roles in apoptosis dysregulation in cancer and leukemia, promoting malignant cell expansion and adding to chemoresistance. (neuroart2006.com)
  • A number of proteins have been identified that are involved during the DNA damage checkpoint response. (genetics.org)
  • In S. cerevisiae , activation of the DNA checkpoint by DNA lesions depends essentially on two sets of proteins, Rad24 and the PCNA-like trimer Rad17-Mec3-Ddc1, on the one hand, and the ATR homolog, the phosphatidylinositol 3-kinase-like Mec1 (in complex with an auxiliary subunit Ddc2), on the other hand (reviewed in references 28 and 58 ). (asm.org)
  • The reduction of Plk1 levels at metaphase kinetochores is similar to the behavior of multiple mitotic checkpoint signaling proteins. (rupress.org)
  • Sirtuins are a conserved family of proteins with homology to silent information regulator 2 (Sir2) of Saccharomyces cerevisiae , initially identified as genetic silencing factors (Rine et al. (springer.com)
  • Multiple cellular roles have been attributed to the breast cancer susceptibility proteins BRCA1 and BRCA2, including a role in DNA repair ( 1 , 2 ). (aacrjournals.org)
  • Together, these results suggest that by targeting checkpoint proteins to kinetochores, Aurora B couples chromosome alignment with anaphase onset. (rupress.org)
  • The binding of these kinases to damaged DNA triggers the recruitment of additional proteins, many of which become phosphorylated and activated to further transduce signals that orchestrate DNA replication, cell cycle control, transcription, repair of damage, and/or survival versus death. (frontiersin.org)
  • Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. (pnas.org)
  • The interaction with certain proteins not only contributes to kinase activation but also governs the spatially and temporally distinct subcellular localization of the three family members. (sciencemag.org)
  • These kinases phosphorylate proteins involved in centrosome duplication and separation, chromosome condensation, spindle assembly and fidelity, chromosome segregation, and cytokinesis, as well as have the ability to behave as oncogenes, providing a compelling link between errors in mitosis and oncogenesis ( 8 ). (aacrjournals.org)
  • INTRODUCTION DNAdamage response (DDR) is a series of signal transduction events triggered by DNA damage in cells =-=(1)-=-, including the recruitment and activation of proteins involved in DNA damage sensing, checkpoint signaling, chromatin remodeling and DNA repair. (psu.edu)
  • Biochimica et Biophysica Acta - Proteins and Proteomics , 1699 (1-2), 139-44. (unibas.ch)
  • Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. (frontiersin.org)
  • These checkpoints arrest cell cycle progression to allow time for repair of DNA lesions before genome duplication in S phase and chromosomal segregation in mitosis and thereby protect against the propagation of progeny cells containing damaged or mutated DNA. (aacrjournals.org)
  • The Aurora/Ipl1 family of protein kinases plays multiple roles in mitosis and cytokinesis. (rupress.org)
  • In higher eukaryotes, syntelic orientations are rare during mitosis ( Nicklas, 1997 ), and therefore, it is unclear whether the kinetochore-SPB resolving activity exhibited by Ipl1 is a universal feature of the Aurora kinase family. (rupress.org)
  • Polo encodes a protein kinase homolog required for mitosis in Drosophila . (nature.com)
  • Glover, D.M., Hagan, I.M. & Tavares, A.A. Polo-like kinases: a team that plays throughout mitosis. (nature.com)
  • van Vugt, M.A. & Medema, R.H. Getting in and out of mitosis with Polo-like kinase-1. (nature.com)
  • Cdk1/cyclinB is widely regarded as the master regulator of mitosis and is responsible for entry into and progression through mitosis as well as mitotic exit ( 1 , 2 ). (sciencemag.org)
  • Mitotic kinases are essential components in the regulation of mitosis and cytokinesis, acting upon various structures involved in mitotic entry, progression, and exit. (aacrjournals.org)
  • Although disregulation of these mitotic kinases has been associated with ovarian cancer prognosis, and one study of polymorphisms found evidence of association with risk and polymorphisms in CDK1 , a key mitotic kinase required for entry into mitosis ( 17 ), the relationship between alterations in these genes and ovarian cancer risk has not been well studied. (aacrjournals.org)
  • Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis. (springer.com)
  • Mitosis is controlled by multiple kinases that drive cell cycle progression and prevent chromosome mis-segregation. (biologists.org)
  • One of the well-characterized molecular pathways for oral carcinogenesis involves activation of the epidermal growth factor receptor, which in turn initiates the ras/ mitogen-activated protein kinase and PI3K/Akt-signaling cascades ( 9 , 10 ). (aacrjournals.org)
  • The genetic alteration and constitutive activation of oncogenic pathways can elicit unscheduled progression into the cell cycle, leading to DNA damage checkpoint activation either directly or indirectly via formation of DNA double-strand breaks ( 5 , 6 , 8 ). (aacrjournals.org)
  • Cells respond to DNA damage by activating a complex network of the so-called checkpoint pathways to delay their cell-cycle progression and repair the defects. (nih.gov)
  • In this review we integrate findings on the emerging mechanisms of activation, the signalling pathways and the spatio-temporal organization of the intra-S-phase DNA-damage checkpoint and its impact on the cell-cycle machinery, and discuss its biological significance. (nih.gov)
  • When exposed to ionizing radiation (IR), eukaryotic cells activate checkpoint pathways to delay the progression of the cell cycle. (nih.gov)
  • Eukaryotic cell cycle transitions are closely regulated by checkpoint signaling pathways. (aacrjournals.org)
  • In Saccharomyces cerevisiae , double-strand breaks (DSBs) activate DNA checkpoint pathways that trigger several responses including a strong G 2 /M arrest. (asm.org)
  • In the face of DNA damage, the genomic integrity of mammalian cells is maintained by activating signaling pathways called DNA damage checkpoints. (aacrjournals.org)
  • A hallmark of tumor cells is an inability to control their proliferation, which implies that these cells are capable of bypassing cell cycle checkpoints and regulation by tumor suppressor signaling pathways. (colorado.edu)
  • Relapsed cancers after radiation and chemotherapy, in general, show defects in DNA damage-induced cell death pathways, particularly, p53-dependent pathways via genetic mutations or epigenetic alternations ( 1, 2 ). (aacrjournals.org)
  • Therefore, the major checkpoint in the cell cycle is the restriction (R) point between G1 and S phases, prior to DNA duplication, at which the cycle progresses depending on mitogenic or inhibitory factors such as DNA damage and signals from various signaling pathways. (antibodies-online.com)
  • Currently, dysregulation of metabolic pathways, including fatty acid metabolic pathways, is considered as a risk factor for promoting breast cancer progression [ 2 ]. (mdpi.com)
  • The mitogen-activated protein kinase kinase (MAPKK) 1 / MAP kinase cascade is thought to be important for a wide variety of signal transduction pathways ( 2 , 4 , 24 , 25 , 29 , 30 ). (rupress.org)
  • Latex of Euphorbia antiquorum-induced S-phase arrest via active ATM kinase and MAPK pathways in human cervical cancer HeLa cells. (sigmaaldrich.com)
  • This study, therefore, revealed that EA could downregulate topoisomerase, and activate ATM kinase, which then induce parallel Chk 1/2 and MAPK signaling pathways to promote the degradation of Cdc25A to induced S-phase arrest in human cervical cancer HeLa cells. (sigmaaldrich.com)
  • Cell-cycle checkpoints are signal-transduction pathways required to maintain genomic stability in dividing cells. (biologists.org)
  • Cell-cycle checkpoints are regulatory pathways that monitor the integrity and replication status of the genome before cells commit to either replicate or segregate their DNA ( Hartwell and Weinert, 1989 ). (biologists.org)
  • The CIN phenotype has been associated with rare mutations in checkpoint genes ( 3 - 6 ) or decreased protein levels of checkpoint components ( 4 , 6 - 8 ). (pnas.org)
  • Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined. (aacrjournals.org)
  • Here we tested the hypothesis that inherited variation in genes encoding mitotic kinases increases the risk of invasive epithelial ovarian cancer. (aacrjournals.org)
  • Mutations of mitotic checkpoint genes in human cancers. (springer.com)
  • One of the evolutionarily conserved genes involved in checkpoint control is Checkpoint kinase 1 ( Chk1 ). (biologists.org)
  • Previous studies have demonstrated that liver cancer initiation may be due to alterations in circadian rhythmic genes, including PER3 ( 23 ) and CRY genes, and casein kinases ( 24 ). (spandidos-publications.com)
  • The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. (frontiersin.org)
  • SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. (springer.com)
  • Deletion in mice of one allele of Mad2, Bub3 , or BubR1 compromises the mitotic checkpoint, yielding higher rates of chromosome missegregation and spontaneous (Mad2) or carcinogen-induced (Bub3 and BubR1) tumors ( 9 - 11 ). (pnas.org)
  • The cleared supernatants were equalized for protein content, and BubR1 was immunoprecipitated with SBR1.1 antibody (a gift of S. Taylor) coupled to protein G-Sepharose beads for 2 hr at 4°C. Beads were washed twice with lysis buffer and twice with kinase buffer (50 mM Tris, pH 7.5/10 mM MgCl 2 /2 mM sodium vanadate). (pnas.org)
  • Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex. (semanticscholar.org)
  • Catalytic assembly of the mitotic checkpoint inhibitor BubR1-Cdc20 by a Mad2-induced functional switch in Cdc20. (semanticscholar.org)
  • Consistent with this notion, all known SAC transducers, including the protein kinases Mps1, Bub1, and BubR1 and the nonkinase components Mad1, Mad2, and Bub3, associate with unattached kinetochores in prometaphase (for review see Musacchio and Salmon, 2007 ). (pubmedcentralcanada.ca)
  • BUB1 and BUBR1: multifaceted kinases of the cell cycle. (springer.com)
  • PURPOSE: This is a 2-part study of pembrolizumab (MK-3475) in pediatric participants who have either advanced melanoma or a programmed cell death ligand 1 (PD-L1)-positive advanced, relapsed or refractory solid tumor or lymphoma. (cincinnatichildrens.org)
  • We have reported that UCN-01 (7-hydroxystaurosporine) abrogates DNA damage-induced S and G 2 arrest and enhances cytotoxicity selectively in p53 mutant cells, thus providing a potential, tumor-targeted therapy. (aacrjournals.org)
  • 2 Management and treatment of cancer are correlated with the diagnosis and specific characteristics of the tumor, such as hormone production and genetic mutations. (dovepress.com)
  • Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells. (pnas.org)
  • Polo-like kinases (Plks) have several functions in mitotic progression and are upregulated in many tumor types. (nature.com)
  • Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells. (springer.com)
  • 4.5.2 Further Roles of JAK2 in Tumor Growth. (whsmith.co.uk)
  • Genomic instability is common in blast crisis and may contribute to malignant progression and resistance to cell death ( 2 - 5 ). (aacrjournals.org)
  • In response to DNA damage, cells arrest progression through the cell cycle at either G 1 , S, or G 2 . (aacrjournals.org)
  • Progression from one phase to another is controlled by cyclin dependent kinases (CDK) and their activators, cyclins. (antibodies-online.com)
  • Progression through the cell cycle requires the controlled activation of different families of kinases that regulate diverse cellular processes required for cell division. (biologists.org)
  • Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. (springer.com)
  • Aurora kinase B interacts with survivin, borealin and incenp to form the chromosomal passenger complex (CPC), which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. (biologists.org)
  • Chk1 then inactivates the Cdc25C protein phosphatase by phospohorylating Cdc25C at Ser 216 , which promotes its sequestration into the cytoplasm and in turn prevents activation of the cyclin B/Cdc2 mitotic kinase complex, finally resulting in G 2 cell cycle arrest ( 5 ) and suppression of mitotic entry ( 6 ). (aacrjournals.org)
  • Both Rad53 FHA domains are required for DNA damage-dependent Rad53 activation (they both bind the Rad9 adaptor) and probably for transducing the checkpoint signal to some downstream targets ( 7 , 8 , 35 , 36 , 41 , 46 ). (asm.org)
  • Our data show that Bcr-Abl expression limits the ability of the mitotic checkpoint to undergo activation and compromises the postmitotic checkpoint, which normally prevents polyploidization. (aacrjournals.org)
  • Cell cycle events are regulated by the sequential activation and deactivation of cyclin dependent kinases (Cdks) and by proteolysis of cyclins. (acris-antibodies.com)
  • The non-receptor-type tyrosine kinase c-Abl functions as a cytoplasmic signal transducer upon activation of cell-surface receptors. (biochemj.org)
  • The mechanism of action of the three platinum drugs approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as well as structurally related platinum(II) complexes, can be divided into four distinct sequential processes: (i) cellular uptake, (ii) aquation/activation, (iii) DNA platination, and (iv) cellular processing leading to apoptosis ( figure 2 ). (royalsocietypublishing.org)
  • Activation of the Aurora kinases occurs by multiple distinct mechanisms, including autophosphorylation of their T loops and protein binding ( 4 ). (sciencemag.org)
  • In Xenopus laevis egg cell cycle extracts that mimic early embryonic cell cycles, activation of MAP kinase and MAP kinase kinase occurs in M phase, slightly behind that of maturation promoting factor. (rupress.org)
  • Like in the mock-treated extracts, the periodic activation and deactivation of MPF occurred normally in the MAP kinase-depleted extracts, suggesting that MAP kinase is dispensable for the normal M phase entry and exit in vitro. (rupress.org)
  • In addition, we show that strong activation of MAP kinase by the addition of a constitutively active MAP kinase kinase kinase in the absence of sperm nuclei and nocodazole, induced mitotic arrest in the extracts. (rupress.org)
  • Therefore, activation of MAP kinase alone is sufficient for inducing the mitotic arrest in vitro. (rupress.org)
  • In Xenopus unfertilized eggs which are arrested at the second meiotic metaphase, MAP kinase is fully activated, whereas in somatic or early embryonic cell cycles marked activation of MAP kinase at M phase has not been detected, although several reports observed the existence of an activated MAP kinase or an activated MAP kinase-like molecule in M phase ( 14 , 31 ). (rupress.org)
  • It has been previously reported that herpes simplex virus type 1 (HSV-1) infection induces activation of protein kinase activity of ATM and hyperphosphorylation of transcription factor, Sp1. (asm.org)
  • S2 cells display Grp/DChk1-dependent and Dmnk/DChk2-independent cell-cycle-checkpoint activation in response to hydroxyurea and ionizing radiation. (biologists.org)
  • 4.5.1 Activation and Known Mutations and Fusions of the JAKFamily of Tyrosine Kinases. (whsmith.co.uk)
  • 5.5 Protein Kinase C. 5.5.1 PKC Activation. (whsmith.co.uk)
  • See " A chemical tool box defines mitotic and interphase roles for Mps1 kinase " on page 21. (pubmedcentralcanada.ca)
  • In this study, we use chemical genetics to show that the protein kinase Mps1 regulates both aspects of the SAC. (pubmedcentralcanada.ca)
  • Human MPS1 -null cells were generated via gene targeting and reconstituted with either the wild-type kinase (Mps1 wt ) or a mutant version (Mps1 as ) sensitized to bulky purine analogues. (pubmedcentralcanada.ca)
  • In response to DNA damage, Chk1, a serine/threonine kinase, is responsible for cell cycle arrest to prevent damaged cells from progressing through the cell cycle. (genetics.org)
  • The Cdc25A phosphatase activates the cyclin-dependent kinase 2 (Cdk2) needed for DNA synthesis, but becomes degraded in response to DNA damage or stalled replication. (nih.gov)
  • Regulates cell cycle checkpoints and apoptosis in response to DNA damage, particularly to DNA double-strand breaks. (abcam.com)
  • CHK 1 and CHK 2 both function as essential components in the G2 DNA damage checkpoint by phosphorylating CDC25C in response to DNA damage. (acris-antibodies.com)
  • ProNAi Therapeutics has obtained an exclusive license from the CRT Pioneer Fund for worldwide rights to develop and commercialize PNT737, a small-molecule inhibitor of checkpoint kinase 1 (Chk1). (genengnews.com)
  • VANCOUVER , Sept. 27, 2016 /CNW/ - ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage drug development company advancing targeted therapeutics for the treatment of patients with cancer, today announced that it has obtained an exclusive license from the CRT Pioneer Fund LP for worldwide rights to develop and commercialize PNT737 (formerly CCT245737), a highly selective, orally available, small molecule inhibitor of Checkpoint kinase 1 (Chk1). (newswire.ca)
  • CK2 (casein kinase 2) is a serine/threonine-selective protein kinase that has been involved in a variety of cellular processes such as DNA repair, cell cycle control and circadian rhythm regulation. (biomedcentral.com)
  • CK2 (casein kinase 2) is an ubiquitously expressed and highly conserved serine/threonine protein kinase that forms a tetramer containing two catalytic (α and/or α´) subunits and two regulatory β subunits [ 1 ]. (biomedcentral.com)
  • The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. (frontiersin.org)
  • Constitutively targeting Plk1 to kinetochores maintained high activity at metaphase, leading to reduced interkinetochore tension and intrakinetochore stretch, a checkpoint-dependent mitotic arrest, and accumulation of microtubule attachment errors. (rupress.org)
  • Cells with a compromised mitotic checkpoint undergo mitotic slippage associated with premature cyclin B1 degradation, chromatin decondensation, and arrest at a postmitotic checkpoint (tetraploid checkpoint) to prevent polyploidization. (aacrjournals.org)
  • However, Gö6976 potently abrogated S and G 2 arrest and enhanced the cytotoxicity of the topoisomerase I inhibitor SN38 only in p53-defective cells. (aacrjournals.org)
  • Importantly, Gö6976 was nearly as potent at abrogating S and G 2 arrest in human serum, a property not possessed by UCN-01. (aacrjournals.org)
  • Many cancer chemotherapy drugs currently in use ( e.g. , cisplatin, mitomycin C, camptothecin, and etoposide) are DNAdamaging agents and arrest cells in the G 1 , S, or G 2 phases of the cell cycle. (aacrjournals.org)
  • The G 1 arrest is dependent upon wild-type p53 activity, whereas S and G 2 arrest do not require p53, so cells mutated for p53 (about 50% of tumors) arrest primarily in S or G 2 in response to damage. (aacrjournals.org)
  • For example, circ-Foxo3 can inhibit CDK2 (cell-dependent kinase 2) and induce cell cycle arrest through a circ-Foxo3-p21-CDK2 ternary complex 16 . (nature.com)
  • In Xenopus laevis , for example, this classical MAP kinase cascade has been shown to play a crucial role in meiotic cell cycles during oocyte maturation, metaphase arrest of unfertilized eggs, and early embryonic development ( 5 , 7 , 9 - 13 , 15 - 18 , 26 , 32 ). (rupress.org)
  • We have previously provided evidence that the phosphatases Ptc2 and Ptc3 of the protein phosphatase 2C type are required for DNA checkpoint inactivation after a DSB and probably dephosphorylate the checkpoint kinase Rad53. (asm.org)
  • We found that Ckb1 and Ckb2, the regulatory subunits of the protein kinase CK2, are necessary for the in vivo interaction between Ptc2 and the Rad53 FHA1 domain, that Ckb1 binds Ptc2 in vitro and that ckb1 Δ and ckb2 Δ mutants are defective in adaptation and recovery after a DSB. (asm.org)
  • Rad53 plays a central part in S. cerevisiae DNA checkpoint: it controls the majority of the DNA damage responses and rad53 Δ cells are strongly hypersensitive to all genotoxic stresses. (asm.org)
  • A) In vitro kinase assay was performed by recombinant Rph1 or BSA incubated with or without V5-IP WT or KD Rad53 supplied by γ32P-ATP. (nih.gov)
  • To test whether Rph1 is a substrate of Rad53, we performed an in vitro kinase assay by incubating IP-activated Rad53 (WT or KD) with recombinant Rph1. (nih.gov)
  • Potent inhibitor of the tyrosine kinases c-Src, fibroblast growth factor receptor 1 (FGFR1), and platelet-derived growth factor receptor β (PDGFR β ) (IC 50 values are 8.4, 39.3 and 98.3 nM respectively). (rndsystems.com)
  • 2.1 Ligand Binding to Receptor Tyrosine Kinases. (whsmith.co.uk)
  • Recent studies in this protein kinase family indicate an important role for ATM and ATR in a meiotic surveillance mechanism that may regulate proper chromosome transmission. (nih.gov)
  • Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission. (nih.gov)
  • Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. (frontiersin.org)
  • A compromised mitotic checkpoint, the primary mechanism for ensuring that each new cell receives one copy of every chromosome, has been implicated as a contributor to carcinogenesis. (pnas.org)
  • Colorectal cancer cells that have an accelerated rate of chromosomal gains and losses [referred to as chromosome instability (CIN)] have a weaker mitotic checkpoint than similarly aggressive cancer cells with a stable chromosome content but which have microsatellite instability (MIN) from errors in DNA repair ( 1 - 3 ). (pnas.org)
  • Polo-like kinase-1 (Plk1) is a highly conserved kinase with multiple mitotic functions. (rupress.org)
  • Similarly, overexpression of polo-like kinases, such as PLK1 and PLK2 , have also been shown to correlate with prognosis, histologic grade, and clinical stage in ovarian cancer ( 14-16 ). (aacrjournals.org)
  • Indeed, QNC reduces Chk1/2 expression under p53-impaired cancer cells and induces cell death in the G 2 -M phase. (aacrjournals.org)
  • Defects in the IR-induced S-phase checkpoint cause 'radioresistant DNA synthesis', a phenomenon that has been identified in cancer-prone patients suffering from ataxia-telangiectasia, a disease caused by mutations in the ATM gene. (nih.gov)
  • The protein encoded by this gene is a member of the Ser/Thr protein kinase family. (antibodies-online.com)
  • This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2. (antibodies-online.com)
  • The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (antibodies-online.com)
  • Our study demonstrates that the histone demethylase Rph1 is associated with a specific chromatin locus and modulates histone modifications to repress a DNA damage responsive gene under control of damage checkpoint signaling. (nih.gov)
  • The ataxia telangiectasia-mutated (ATM) protein, a member of the related phosphatidylinositol 3-like kinase family encoded by a gene responsible for the human genetic disorder ataxia telangiectasia, regulates cellular responses to DNA damage and viral infection. (asm.org)
  • Background: Phosphoactivation of a DNA damage response molecule checkpoint kinase 2 (pChk2) may be a marker of oral epithelial cells that have entered the precancerous and squamous cell carcinoma (SCC) stages. (aacrjournals.org)
  • An estimated 400,000 people worldwide are newly diagnosed with oral squamous cell carcinoma (SCC) annually, which accounts for 5% of all cancers in men and 2% in women ( 1 ). (aacrjournals.org)
  • It is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. (antibodies-online.com)
  • Because c-Abl promotes expression of the cyclin-dependent kinase inhibitor p21 upon stimulation with the DNA-damaging agent Adriamycin (doxorubicin), we analysed the involvement of JunB in Adriamycin-induced p21 expression. (biochemj.org)
  • The families of cyclin-dependent (Cdk), Aurora, and Polo-like (Plk) kinases have emerged as the primary regulators of cell division. (sciencemag.org)
  • Cyclin-dependent kinases (CDKs) is a family of serine/threonine kinases. (psu.edu)
  • The leading etiologic factors implicated in oral cancer, such as tobacco, alcohol, and chronic inflammation, are thought to promote DNA damage either by direct DNA modification or by abnormalities of the cell cycle checkpoint machinery. (aacrjournals.org)
  • Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. (nih.gov)
  • The maintenance of genomic integrity after DNA damage depends on the coordinated action of the DNA repair system and cell cycle checkpoint controls. (sciencemag.org)
  • In combination with docetaxel, PF-00477736 abrogates the mitotic checkpoint, as well as the DNA damage checkpoint, and results in sensitization to docetaxel. (aacrjournals.org)
  • In normal cells, DNA damage activates the p53-dependent G 1 checkpoint and triggers DNA repair. (aacrjournals.org)
  • Cancer cells often depend on activated Chk1, a central cell cycle checkpoint regulator in the DDR network, as a strategy to survive and replicate despite accumulating extensive DNA damage due to replicative stress or in response to chemotherapeutic intervention. (newswire.ca)
  • Mediator of DNA damage checkpoint 1 (MDC1) is an important protein in the Ataxia telangiectasia mutated (ATM) mediated double stranded DNA break (DSB) repair pathway. (biomedcentral.com)
  • Belongs to the protein kinase superfamily. (abcam.com)
  • 1.3 A Tour of the Human Protein Kinase Superfamily. (whsmith.co.uk)
  • However, a checkpoint response is shown here to be essential for cell survival, including that of chromosomally instable colorectal cancer cells. (pnas.org)
  • 2 Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, and Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. (sciencemag.org)
  • This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. (antibodies-online.com)
  • The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. (hmdb.ca)
  • Bearing in mind the proposed role of BRCA1 in the SAC, here we investigated the influence of Bcr-Abl expression on the BRCA1 level as well as competence and efficacy of the mitotic checkpoint. (aacrjournals.org)
  • We found that Bcr-Abl caused strong downregulation of BRCA1 and decreased the expression of the mitotic checkpoint components. (aacrjournals.org)
  • Whereas inherited mutations in BRCA1 and BRCA2 account for 50% of ovarian cancer cases in families with 2 or more confirmed cases ( 5 ), the remaining unexplained familial and sporadic ovarian cancer risk is likely, in part, attributable to common, low-penetrance alleles ( 6 ). (aacrjournals.org)
  • The premature termination of M phase was found to be a consequence of precocious inactivation of SAC caused by a direct inhibitory effect of the compound on Aurora B kinase in vitro and in cells. (oup.com)
  • The compound also targets Aurora A kinase and tubulin in vitro and in cells, which can explain the observed spindle anomalies. (oup.com)
  • Based on the results presented here, we hypothesize that ROS production in wat1 -null mutant cells generates DNA fragmentation that could trigger a checkpoint response and that, in the absence of checkpoint kinase Chk1, the cells exhibit severe growth defects leading to a synthetic lethal phenotype. (genetics.org)
  • In mammalian cells, four protein kinases form the PI3-kinase-related protein kinase (PIK) superfamily. (nih.gov)
  • Generation of polyploids took place also in K562 cells after mitotic checkpoint impairment. (aacrjournals.org)
  • A consequence of these dysfunctions is the generation of aneuploid cells on prolonged checkpoint failure and resistance to chemotherapeutics called microtubule poisons. (aacrjournals.org)
  • Colcemid (KaryoMax, Invitrogen) was added to cells at a final concentration of 50 ng/ml and re-added every 2 days in experiments where treatment exceeded 2 days. (pnas.org)
  • T98G cells were transfected with indicated siRNA plasmids for 8 hr, subjected to double 2 mM thymidine block, and released for 9.5 hr. (pnas.org)
  • Figure 2: Mitotic abnormalities induced by cyclapolin 1 in HeLa cells. (nature.com)
  • Indeed, errors in the choreography of the processes controlled by mitotic kinases disrupt successful division of mammalian cells and can lead to aneuploidy, genetic instability, and cancer. (aacrjournals.org)
  • Radiosensitization of p53 mutant cells by PD0166285, a novel G 2 checkpoint abrogator. (rndsystems.com)
  • Here, we report the function of these checkpoint kinases, referred to as Grp/DChk1 and Dmnk/DChk2 in Drosophila Schneider's cells, and identify an upstream regulator as well as downstream targets of Grp/DChk1. (biologists.org)
  • First, we demonstrate that S2 cells are a suitable model for G 2 /M checkpoint studies. (biologists.org)
  • We conclude that Grp/DChk1, and not Dmnk/DChk2, is the main effector kinase involved in G 2 /M checkpoint control in Drosophila cells. (biologists.org)
  • The reduced activity of Aurora B kinase resulted in polyploidy and suppression of cancer cell viability. (oup.com)
  • Here, we describe ZM447439, a novel selective Aurora kinase inhibitor. (rupress.org)
  • In mammals, the family of Aurora kinases consists of three paralogs, Aurora A, B, and C ( 3 ), which share a high degree of sequence conservation in their kinase domains. (sciencemag.org)
  • Aurora A has been implicated in the G 2 -M transition ( 5 - 9 ), centrosome maturation and separation, as well as the formation of a bipolar spindle ( 4 ). (sciencemag.org)
  • Mitotic kinases include members of the Aurora, Polo-like, and Nek families, as well as individual kinases involved in mitotic checkpoints, mitotic exit, and cytokinesis. (aacrjournals.org)
  • Within the Aurora kinase family, the overexpression of both AURKA and AURKB has been associated with poor prognosis in epithelial ovarian cancers ( 10-13 ). (aacrjournals.org)
  • Re-expression of wild-type, but not kinase-dead, aurora C rescues this defect, suggesting functional overlap between these two kinases. (biologists.org)
  • Aurora kinases participate in multiple processes during the mammalian cell cycle ( Carmena and Earnshaw, 2003 ). (biologists.org)
  • Ovarian carcinomas comprise a diverse group of neoplasms that demonstrate distinct clinicopathological features and unique molecular genetic aberrations with respect to different histologic subtypes [ 1 , 2 ]. (hindawi.com)
  • Kumagai, A. & Dunphy, W.G. Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. (nature.com)
  • TGF-β signals via two receptor Ser/Thr protein kinases, termed type I and type II TGF-β receptors. (colorado.edu)
  • 2.1.2 Insulin:Insulin Receptor and IGF1:IGF1R. (whsmith.co.uk)
  • Central to this network are protein kinases of the PIKK (phosphoinositide 3-kinase-related protein kinase) family, like ATM (ataxia-telangiectasia mutated), ATR (ATM and Rad3-related), that work as sensors and transducers. (genetics.org)
  • DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ataxia telangiectasia and Rad 3 related) are thought to participate in responses to nuclear cues that activate DNA rearrangements or cell cycle arrests. (nih.gov)