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.
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.
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.
Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. It is found primarily in GERM CELLS in the TESTIS, and may mediate CHROMOSOME SEGREGATION during SPERMATOGENESIS.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Agents that inhibit PROTEIN KINASES.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
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.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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)
A cell line derived from cultured tumor cells.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
Seven membered heterocyclic rings containing a NITROGEN atom.
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.
Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.
BENZOIC ACID amides.
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.
The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
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.
The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
The process by which the CYTOPLASM of a cell is divided.
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.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
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.
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.
A benign neoplasm derived from mesodermal cells that form cartilage. It may remain within the substance of a cartilage or bone (true chondroma or enchondroma) or may develop on the surface of a cartilage (ecchondroma or ecchondrosis). (Dorland, 27th ed; Stedman, 25th ed)
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.
Agents which affect CELL DIVISION and the MITOTIC SPINDLE APPARATUS resulting in the loss or gain of whole CHROMOSOMES, thereby inducing an ANEUPLOIDY.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
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.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
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.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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 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.
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.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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 fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.
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.
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.
A small whitish spot on the surface of the EGG YOLK where cleavage begins. Upon fertilization the cytoplasm streams from the vegetal pole away from the yolk to the animal pole where cleavage will occur. This germinal area eventually flattens into a layer of cells (BLASTODERM) that covers the yolk completely.
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.
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).
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A family of rat kangaroos found in and around Australia. Genera include Potorous and Bettongia.
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 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.
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.
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.
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.
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.
Cellular functions, mechanisms, and activities.
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.
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.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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 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 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.
An amorphous region of electron dense material in the cytoplasm from which the MICROTUBULES polymerization is nucleated. The pericentriolar region of the CENTROSOME which surrounds the CENTRIOLES is an example.
The degree of replication of the chromosome set in the karyotype.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
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.
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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.
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 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 cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
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.
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.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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 action of a drug in promoting or enhancing the effectiveness of another drug.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
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.
Established cell cultures that have the potential to propagate indefinitely.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.
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.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Phylum in the domain Eukarya, comprised of animals either with fully developed backbones (VERTEBRATES), or those with notochords only during some developmental stage (CHORDATA, NONVERTEBRATE).
The rate dynamics in chemical or physical systems.
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.
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.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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 order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats.
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.
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 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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
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.
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.
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.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
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 non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Proteins prepared by recombinant DNA technology.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.

Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. (1/1165)

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis.  (+info)

The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast. (2/1165)

Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.  (+info)

Novel protein kinases Ark1p and Prk1p associate with and regulate the cortical actin cytoskeleton in budding yeast. (3/1165)

Ark1p (actin regulating kinase 1) was identified as a yeast protein that binds to Sla2p, an evolutionarily conserved cortical actin cytoskeleton protein. Ark1p and a second yeast protein, Prk1p, contain NH2-terminal kinase domains that are 70% identical. Together with six other putative kinases from a number of organisms, these proteins define a new protein kinase family that we have named the Ark family. Lack of both Ark1p and Prk1p resulted in the formation of large cytoplasmic actin clumps and severe defects in cell growth. These defects were rescued by wild-type, but not by kinase-dead versions of the proteins. Elevated levels of either Ark1p or Prk1p caused a number of actin and cell morphological defects that were not observed when the kinase-dead versions were overexpressed instead. Ark1p and Prk1p were shown to localize to actin cortical patches, making these two kinases the first signaling proteins demonstrated to be patch components. These results suggest that Ark1p and Prk1p may be downstream effectors of signaling pathways that control actin patch organization and function. Furthermore, results of double-mutant analyses suggest that Ark1p and Prk1p function in overlapping but distinct pathways that regulate the cortical actin cytoskeleton.  (+info)

Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. (4/1165)

A centrosomal serine/threonine kinase, AIK1(3)/breast tumor amplified kinase/aurora2, which was recently identified as an oncogene, shows high amino acid identity with chromosome segregation kinases, fly Aurora, and yeast Ipl1. Immunohistochemical analyses of invasive ductal adenocarcinomas of the breast revealed that overexpression of AIK1 was observed in 94% of the cases, irrespective of the histopathological type, whereas the protein was not detected in normal ductal and lobular cells. Benign breast lesions including fibrocystic disease and fibroadenoma (epithelial components) displayed weakly detectable AIK1 expression in part of the lesions. This is the first immunohistochemical report of AIK1 expression in primary human breast carcinomas. Although the physiological function(s) of AIK1 kinase during cell division remains to be determined, the markedly high positivity of AIK1 staining in the cancer lesions suggested a possible involvement of its overexpression in the tumorigenesis of some of breast cancer cells.  (+info)

The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XlEg5. (5/1165)

We have previously reported on the cloning of XlEg5, a Xenopus laevis kinesin-related protein from the bimC family (Le Guellec, R., Paris, J., Couturier, A., Roghi, C., and Philippe, M. (1991) Mol. Cell. Biol. 11, 3395-3408) as well as pEg2, an Aurora-related serine/threonine kinase (Roghi, C., Giet, R., Uzbekov, R., Morin, N., Chartrain, I., Le Guellec, R., Couturier, A., Doree, M., Philippe, M., and Prigent, C. (1998) J. Cell Sci. 111, 557-572). Inhibition of either XlEg5 or pEg2 activity during mitosis in Xenopus egg extract led to monopolar spindle formation. Here, we report that in Xenopus XL2 cells, pEg2 and XlEg5 are both confined to separated centrosomes in prophase, and then to the microtubule spindle poles. We also show that pEg2 co-immunoprecipitates with XlEg5 from egg extracts and XL2 cell lysates. Both proteins can directly interact in vitro, but also through the two-hybrid system. Furthermore immunoprecipitated pEg2 were found to remain active when bound to the beads and phosphorylate XlEg5 present in the precipitate. Two-dimensional mapping of XlEg5 tryptic peptides phosphorylated in vivo first confirmed that XlEg5 was phosphorylated by p34(cdc2) and next revealed that in vitro pEg2 kinase phosphorylated XlEg5 on the same stalk domain serine residue that was phosphorylated in metabolically labeled XL2 cells. The kinesin-related XlEg5 is to our knowledge the first in vivo substrate ever reported for an Aurora-related kinase.  (+info)

Stu-7/air-2 is a C. elegans aurora homologue essential for chromosome segregation during embryonic and post-embryonic development. (6/1165)

We have isolated a new sterile uncoordinated C. elegans mutant, stu-7, which is defective in post-embryonic cell divisions in a regionally-specific fashion. The anterior of the worm is relatively unaffected whereas the mid-body and/or posterior are markedly thin, often resulting in worms having a central 'waist'. We have cloned stu-7 and found that it encodes a member of the recently expanding aurora sub-family of serine/threonine kinases. Elimination of maternal as well as zygotic stu-7 expression reveals that stu-7 is essential for mitosis from the first embryonic cell cycle onwards and is required for chromosome segregation though not for centrosome separation or for setting up a bipolar spindle. Multicopy expression of stu-7 also causes mitotic defects, suggesting that the level of this protein must be tightly controlled in order to maintain genetic stability during development.  (+info)

Cdc20 associates with the kinase aurora2/Aik. (7/1165)

Cdc20/fizzy family proteins are involved in activation of the anaphase-promoting complex/cyclosome, which catalyzes the ubiquitin-dependent proteolysis of cell cycle regulatory proteins such as anaphase inhibitors and mitotic cyclins, leading to chromosome segregation and exit from mitosis. Previous work has shown that human Cdc20 (hCdc20/p55CDC) associates with one or more kinases. We report here that Cdc20-associated myelin basic protein kinase activity peaks sharply in early M phase (embryonic cells) or in G2 phase (somatic cells). In HeLa cells, Cdc20 is associated with the kinase aurora2/Aik. Aurora2/Aik is a member of the aurora/Ipl1 family of kinases that, like Cdc20, previously has been shown to be localized at mitotic spindle poles and is involved in regulating chromosome segregation and maintaining genomic stability. The demonstration that Cdc20 is associated with aurora2/Aik suggests that some function of Cdc20 is carried out or regulated through its association with aurora2/Aik.  (+info)

Sli15 associates with the ipl1 protein kinase to promote proper chromosome segregation in Saccharomyces cerevisiae. (8/1165)

The conserved Ipl1 protein kinase is essential for proper chromosome segregation and thus cell viability in the budding yeast Saccharomyces cerevisiae. Its human homologue has been implicated in the tumorigenesis of diverse forms of cancer. We show here that sister chromatids that have separated from each other are not properly segregated to opposite poles of ipl1-2 cells. Failures in chromosome segregation are often associated with abnormal distribution of the spindle pole-associated Nuf2-GFP protein, thus suggesting a link between potential spindle pole defects and chromosome missegregation in ipl1 mutant cells. A small fraction of ipl1-2 cells also appears to be defective in nuclear migration or bipolar spindle formation. Ipl1 associates, probably directly, with the novel and essential Sli15 protein in vivo, and both proteins are localized to the mitotic spindle. Conditional sli15 mutant cells have cytological phenotypes very similar to those of ipl1 cells, and the ipl1-2 mutation exhibits synthetic lethal genetic interaction with sli15 mutations. sli15 mutant phenotype, like ipl1 mutant phenotype, is partially suppressed by perturbations that reduce protein phosphatase 1 function. These genetic and biochemical studies indicate that Sli15 associates with Ipl1 to promote its function in chromosome segregation.  (+info)

Recently, Aurora kinases (A, B, and C/serine threonine kinases) gained much attention due to their implication in several types of cancers. Aurora kinases are involved in multiple functions in mitosis. Aurora A is involved in mitotic entry, separation of centriole pairs, accurate bipolar spindle assembly, alignment of metaphase chromosomes and completion of cytokinesis. Aurora B is a chromosomal passenger protein involved in the regulation of chromosomal orientation, and regulating the association between kinetochores and microtubules, and cytokinesis. Aurora C exhibits similar functions to those assigned to Aurora B and is required for cytokinesis. The above mentioned functions are directly involved in maintaining genomic stability. The relation between Aurora kinases overexpression and transformation has been reported in many cancers. Aurora A was shown to overexpress in colorectal, renal, melanoma, and breast cancers. Mainly Aurora B was shown to overexpress in colorectal cancer. Aurora B was ...
Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase-dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT-MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of ...
Whether aurora A or aurora B is the better anticancer drug target is a matter of debate (8). At least two groups have directly addressed this question in the laboratory. Warner et al. (36) compared the effects of aurora A and aurora B antisense oligonucleotides in pancreatic cancer cells and found that aurora A-targeted therapy may be preferable to aurora B targeting, as shown by mitotic arrest and the rapid induction of apoptosis. Girdler et al. (37) compared the effects of RNA interference and small molecules targeting aurora A versus aurora B in colon cancer cells and found that the cells tested were extremely sensitive to aurora B inhibition. Interestingly, dual inhibition of aurora A and B results in phenotypes identical to inactivation of aurora B alone (28). Using RNA interference experiments, Yang et al. (38) showed that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy, indicating that aurora B is responsible for mitotic arrest in the absence ...
Whether aurora A or aurora B is the better anticancer drug target is a matter of debate (8). At least two groups have directly addressed this question in the laboratory. Warner et al. (36) compared the effects of aurora A and aurora B antisense oligonucleotides in pancreatic cancer cells and found that aurora A-targeted therapy may be preferable to aurora B targeting, as shown by mitotic arrest and the rapid induction of apoptosis. Girdler et al. (37) compared the effects of RNA interference and small molecules targeting aurora A versus aurora B in colon cancer cells and found that the cells tested were extremely sensitive to aurora B inhibition. Interestingly, dual inhibition of aurora A and B results in phenotypes identical to inactivation of aurora B alone (28). Using RNA interference experiments, Yang et al. (38) showed that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy, indicating that aurora B is responsible for mitotic arrest in the absence ...
Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. Chromosomal segregation during mitosis as well as meiosis is regulated by kinases and phosphatases. The Aurora kinases associate with microtubules during chromosome movement and segregation. Aurora kinase B localizes to microtubules near kinetochores, specifically to the specialized microtubules called K-fibers, and Aurora kinase A (MIM 603072) localizes to centrosomes (Lampson et al., 2004).[supplied by OMIM] In cancerous cells, over-expression of these enzymes causes unequal distribution of genetic information, creating aneuploid cells, a hallmark of cancer. In 1998, Aurora kinase B was identified in humans by a polymerase chain reaction screen for kinases that are overexpressed in cancers. In the same year, rat Aurora kinase B was identified in a screen designed to find kinases that altered S. cerevisiae proliferation when overexpressed. The expression and activity of Aurora B are regulated ...
Aurora kinases play distinct roles during mitosis, with Aurora A being essential for centrosome maturation and spindle assembly and Aurora B functioning at kinetochores in chromosome attachment and at the end of mitosis in cytokinesis (reviewed in refs. 3, 4).. Inhibition of Aurora kinases is emerging as a new strategy for anticancer therapy, and several small-molecule inhibitors have entered clinical trials. In this report, we describe the biochemical and pharmacologic activity profile of PHA-739358, a spectrum-selective small-molecule kinase inhibitor, which was identified during a screen for inhibitors of Aurora kinases. In most of the cell lines tested, cells fail to divide, resulting in polyploidy without a strong impact on the timing of mitosis (data not shown) and finally leading to a reduction in viability. In some cell lines, an increased apoptosis was seen. This speaks for a dominant Aurora B kinase-related mechanism of action for inhibition because Aurora A inhibition would rather ...
Aurora kinases play distinct roles during mitosis, with Aurora A being essential for centrosome maturation and spindle assembly and Aurora B functioning at kinetochores in chromosome attachment and at the end of mitosis in cytokinesis (reviewed in refs. 3, 4).. Inhibition of Aurora kinases is emerging as a new strategy for anticancer therapy, and several small-molecule inhibitors have entered clinical trials. In this report, we describe the biochemical and pharmacologic activity profile of PHA-739358, a spectrum-selective small-molecule kinase inhibitor, which was identified during a screen for inhibitors of Aurora kinases. In most of the cell lines tested, cells fail to divide, resulting in polyploidy without a strong impact on the timing of mitosis (data not shown) and finally leading to a reduction in viability. In some cell lines, an increased apoptosis was seen. This speaks for a dominant Aurora B kinase-related mechanism of action for inhibition because Aurora A inhibition would rather ...
We have characterised the role played by the aurora-related kinase Ark1 in regulating mitotic progression in fission yeast. In contrast to metazoans, where aurora A is required for spindle formation and aurora B required for both chromosome condensation and cytokinesis, a single aurora kinase, Ark1, is required for mitosis in S. pombe. The phenotypes arising in cells that lack Ark1 suggest that this single kinase is performing functions that are related to the functions of each of the two isoforms in higher systems. The spindle formation defects of ark1.Δ1 cells resemble the consequences of perturbing aurora A function in Drosophila and Xenopus (Glover et al., 1995; Roghi et al., 1998), while the lack of chromosome resolution during anaphase resembles aurora B deficiencies in C. elegans and Drosophila (Adams et al., 2001b; Giet and Glover, 2001; Kaitna et al., 2000; Severson et al., 2000b). Although we failed to detect a requirement for Ark1 during cytokinesis, it remains a possibility that, ...
Aurora kinases are serine/threonine kinases that are essential for cell proliferation. Aurora kinase helps the dividing cell dispense its genetic materials to its daughter cells. Defects in this segregation can cause genetic instability, a condition which is highly associated with tumorigenesis. Three Aurora kinases have been identified in mammalian cells to date, Aurora A, Aurora B, Aurora C. Besides being implicated as mitotic regulators, these three kinases have generated significant interest in the cancer research field due to their elevated expression profiles in many human cancers.
Background: It is known that aurora B, a chromosomal passenger protein responsible for the proper progression of mitosis and cytokinesis, is overexpressed throughout the cell cycle in cancer cells. Overexpression of aurora B produced multinuclearity and induced aggressive metastasis, suggesting that overexpressed aurora B has multiple functions in cancer development. However, the detailed dynamics and functions of overexpressed aurora B are poorly understood. Results: We overexpressed GFP fused aurora B kinase in normal rat kidney epithelial cells. Using spinning disk confocal microscopy, we found that overexpressed aurora B-GFP was predominantly localized in the nucleus and along the cortex as a dot-like or short filamentous structure during interphase. Time-lapse imaging revealed that a cytoplasmic fraction of overexpressed aurora B-GFP was incorporated into the nucleus after cell division. Immunofluorescence showed that the nuclear fraction of overexpressed aurora B did not induce ectopic ...
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer-based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.. ...
SAR156497 is an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy with IC50 = 0.5 nM (Aurora A); 1 nM (Aurora B / incenp); 3 nM (Aurora C / incenp) respectively SAR156497 combines high in vitro potency with satisfactory metabolic stability and limited CYP 3A4 and PDE3 inhibition. In vitro, SAR156497 displayed high antiproliferative activity on a large panel of tumor cell lines without correlation with any particular genetic signature or Aurora kinases expression. It induced significant modulation of Aurora A and Aurora B biomarkers (p-Aurora A and pHH3, respectively) and cell polyploidy, as expected from Aurora A/B inhibitors. In vivo efficacy has been demonstrated on relevant tumor models, but unfortunately, SAR156497 displayed a narrow therapeutic window.
Background: Aurora kinases are promising targets for cancer chemotherapy. Many reports have been published that some cancers overexpress Aurora kinases, which correlates with tumor grade and poor prognosis. Hence Aurora kinases were considered key genes for cancerogenesis and progression. Many Aurora kinase inhibitors(AKI,s) are in various phases of pre-clinical and clinical development and promising anticancer effects have been reported. Tumor resistance remains one of the major problems in chemotherapy.. Objectives: Our work is mainly aimed at identification of potential resistance mechanisms towards CYC116 (new small molecule pan Aurora kinase inhibitor) and ZM447439. The main aims include generation and selection of resistant tumor cell clones, characterization of resistance, cross resistance with other AKI,s and multidrug resistance. Further characterization of the resistant clones included cell cycle analysis, expression and DNA sequencing of Aurora kinases, cellular target inhibition, and ...
Aurora Kinase A Pipeline Review H2 Market 2019. Aurora Kinase A Pipeline Review H2 Market Size by Types, Applications, Major Regions and Major Manufacturers including the capacity, production, price, revenue, cost, gross margin, sales volume, sales revenue, consumption, growth rate, import, export, supply, future strategies.
Aurora kinases comprise a family group of highly conserved serine-threonine proteins kinases that play a pivotal part in the rules of cell routine. from homozygous mutant moms. The mutants recognized were given titles linked to the polar areas, and included not merely but also the similarly famous gene was initially found out in the past due 1980s within a seek out genes regulating cell routine development (Glover, 1989; Glover et al., 1989, 1995). Since that time, Aurora kinases possess emerged as important players in the rules of cell department (for review observe Carmena et al., 2009). The original steady circulation of publications quickly accelerated as paralogs in various species were found out and new features designated to them. The obtaining of elevated degrees of Auroras in malignancy cells soon activated the introduction of little molecule inhibitors of the kinases (Hauf et al., 2003; Harrington et al., 2004). This as well was to become field where research output offers increased ...
The Aurora family of serine-threonine kinases are essential regulators of cell division in mammalian cells. Aurora-A and -B expression and kinase activity is elevated in a variety of human cancers and is associated with high proliferation rates and poor prognosis. AMG 900 is a highly potent and selective pan-aurora kinase inhibitor that has entered clinical evaluation in adult patients with advanced cancers. In mice, oral administration of AMG 900 blocks the phosphorylation of histone H3 on serine-10 (p-Histone H3), a proximal substrate of aurora-B and inhibits the growth of multiple human tumor xenografts, including multidrug-resistant models. In order to establish a preclinical pharmacokinetic-pharmacodynamic (PK-PD) relationship for AMG 900 that could be translated to the clinic, we used flow cytometry and laser scanning cytometry detection platforms to assess the effects on p-Histone H3 inhibition in terms of sensitivity, precision, and specificity, in human tumor xenografts in conjunction with
Recombinant full-length human Aurora B was expressed by baculovirus in Sf9 cells using an N-terminal GST tag. Aurora B is a member of the Aurora kinase family that associates with microtubules during chromosome movement and segregation.
TY - JOUR. T1 - Aurora kinase A promotes inflammation and tumorigenesis in mice and human gastric neoplasia. AU - Katsha, Ahmed. AU - Soutto, Mohammed. AU - Sehdev, Vikas. AU - Peng, Dunfa. AU - Washington, M. Kay. AU - Piazuelo, M. Blanca. AU - Tantawy, Mohammed N.. AU - Manning, H. Charles. AU - Lu, Pengcheng. AU - Shyr, Yu. AU - Ecsedy, Jeffrey. AU - Belkhiri, Abbes. AU - El-Rifai, Wael. PY - 2013/1/1. Y1 - 2013/1/1. N2 - Background & Aims Chronic inflammation contributes to the pathogenesis of gastric tumorigenesis. The aurora kinase A (AURKA) gene is frequently amplified and overexpressed in gastrointestinal cancers. We investigated the roles of AURKA in inflammation and gastric tumorigenesis. Methods We used quantitative real-time reverse transcription polymerase chain reaction, immunofluorescence, immunohistochemistry, luciferase reporter, immunoblot, co-immunoprecipitation, and in vitro kinase assays to analyze AGS and MKN28 gastric cancer cells. We also analyzed Tff1-/- mice, growth of ...
The purpose of this study is to assess the safety and tolerability of MK-0457(VX-680), an Aurora kinase inhibitor, in participants with advanced solid tumors. Bioavailability of the oral formulation will also be assessed. The primary study hypothesis is that administration of MK-0457 is sufficiently safe and tolerated to permit further study ...
OUTLINE: This is an open-label, dose-escalation, multicenter study.. Patients receive Aurora kinase inhibitor AT9283 (AT9283) IV over 24 hours on days 1 and 8 . Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.. Cohorts of 3-6 patients receive escalating doses of AT9283 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose preceding the MTD is the recommended phase II dose (RPTD). Up to 8 additional patients are treated at the RPTD.. Patients treated at the RPTD undergo skin and tumor tissue biopsy and blood collection at baseline and on days 2 and/or 3. Samples are examined by pharmacokinetic and pharmacodynamic analysis, including immunohistochemistry, immunocytochemistry, western blotting, immunoenzyme techniques, flow cytometry, and reverse transcriptase-polymerase chain reaction, for biological markers.. After completion of ...
The IUPHAR/BPS Guide to Pharmacology. aurora kinase inhibitor III ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
This study looks at how well cisplatin and gemcitabine hydrochloride, with or without ATR kinase inhibitor VX-970 works in treating patients with urothelial cancer that has spread to other places in the body. Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. ATR kinase inhibitor VX-970 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin and gemcitabine hydrochloride work better alone or with ATR kinase inhibitor VX-970 in treating patients with urothelial cancer. ...
Aurora B is expressed at high level in primary human colorectal cancers and other cancer cell lines. Sino Biological offers Aurora B protein, Aurora B antibody, Aurora B gene and Aurora B ELISA kit.
Hesperadin is a human Aurora B inhibitor with an IC50 of 40 nM for the prevention of the phosphorylation of substrate. Find all the information about Hesperadin for cell signaling research.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Aurora A (serine/threonine kinase 6) is overexpressed in many pre-invasive and invasive breast carcinomas. High expression of Aurora A is strongly associated with decreased survival in patients with breast cancer, but the molecular mechanisms that underlie Aurora-A-associated malignancy are poorly understood. Here, Kavita Shah and co-workers (p. 2711) use a new chemical genetic approach to identify the pleckstrin-homology-like domain protein PHLDA1 as a putative Aurora A target. The authors confirm previous reports that PHLDA1 is frequently downregulated in primary breast cancers and, in addition, show that PHLDA1 downregulation is associated with oestrogen receptor expression in breast carcinoma. Aurora A directly phosphorylates PHLDA1, which leads to its degradation, but PHLDA1 also negatively regulates Aurora A, thereby setting up a feedback loop. Finally, they show that PHLDA1 upregulation and Aurora A inhibition act synergistically to promote cell death, and that PHLDA1 strongly inhibits ...
At the outset of this work, the existence of a second aurora-like gene in Drosophila, aurora B, was already known (previously named ial; Reich et al. 1999), but there were no known mutations at the locus and the enzyme had not been localized within cells. The proximity of other genes made the prospect of generating such mutations by classical genetic means somewhat daunting and although a model system for the targeted disruption of genes has recently been developed (Rong and Golic 2000), this is also a time-consuming and not yet widely used procedure. In several organisms dsRNAi has offered opportunities for studying the genetic basis of many aspects of cell biology in the absence of mutations in the genes directing these activities. This has been perhaps best demonstrated in C. elegans, where the technique is most widely used (Hunter 1999, Hunter 2000). A simple system for dsRNAi in cultured Drosophila cells not only offers the means of eliminating specific gene expression (Caplen et al. 2000; ...
The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging from the entry into mitosis, centrosome function, mitotic spindle formation, chromosome biorientation and segregation, and cytokinesis. The recent identification of novel bindi …
Once the dose levels reached 190 mg/m2, tests on skin biopsies showed that the drug was inhibiting the aurora B protein - in other words it was beginning to do what we expected it to.. The aurora B protein is responsible for phosphorylating histone H3 - a protein involved in the structure of chromatin (the strands of DNA that make up chromosomes) in cells. Inhibition of aurora B results in the inhibition of phosphorylation of histone H3, thereby blocking that step in cell division. This study shows, for the first time, that the aurora kinase inhibitor PHA-739358 inhibits phosphorylation of histone H3 in the skin of patients, and therewith provides a proof for its (or one of its) mechanisms of action.. The researchers are continuing to recruit patients in order to define the safety of the drug and the recommended dose for subsequent studies. However, they believe the results so far are promising.. The clinical trial has proved the concept that inhibition of the aurora protein disrupts an ...
5648 The Aurora family of serine/threonine kinases (Aurora A, Aurora B, and Aurora C) plays a key role in cells orderly progression through mitosis. Elevated expression levels of Aurora kinases have been detected in a high percentage of melanoma, colon, breast, ovarian, gastric, and pancreatic tumors, and in a subset of these tumors the AURKA locus (20q13) is amplified. SNS-314, a novel aminothiazole-derived urea, is a selective inhibitor of Aurora kinases A, B, and C with IC50 values in the low nanomolar range. SNS-314 potently inhibits cell proliferation and induces polyploidy (, 4N DNA) in a diverse panel of human cancer cell lines. In the present study we investigated the pharmacodynamic effects and in vivo activity of SNS-314 in human tumor xenograft models. SNS-314 displayed potent anti-tumor activity in HCT-116 (colon), PC-3 (prostate), CALU-6 (NSCLC) and MDA-MB-231 (breast) models. Tumor growth inhibition in these xenograft models ranged from 67.5 to 96.6% on a bi-weekly administration ...
Fingerprint Dive into the research topics of The Aurora Kinase A polymorphisms are not associated with recurrencefree survival in prostate cancer patients. Together they form a unique fingerprint. ...
Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells. In this study, x-ray crystal structures of the Aurora A kinase domain delineate redox-sensitive cysteine residues that, upon covalent modification, can allosterically regulate kinase activity and oligomerization state. We showed in both Xenopus laevis egg extracts and mammalian cells that a conserved cysteine residue within the Aurora A activation loop is crucial for Aurora A activation by ...
ributed cell populations in G0 G1, S and G2 M phases. In contrast, OE33 and markedly OE19 and EPC hTERT cells selleck compound had a high G0 G1 phase population, with reduced S and G2 M phase populations. Aurora kinases in normal esophageal epithelial cells and esophageal cancer cells For Aurora A, fluorescence in situ hybridization revealed chromosome 20 polysomy with concomitantly elevated Aurora A gene copy num bers in OE21, OE33 and OE19 cells and an Aurora A gene amplification with up to nine Aurora A gene copies in Kyse 410 cells. In view of their Aurora A gene amplification, Kyse 410 cells also showed highest Aur ora A mRNA and high protein expression. In contrast, OE21, OE33 and OE19 cells exhibited lower Aurora A mRNA expression, despite chromosome 20 polysomy.. Still, high Aurora A protein expression was seen in OE33, but not OE21 and OE19 cells. Active Aurora A was hardly detectable in Inhibitors,Modulators,Libraries immunoblot analysis, but weak Aur ora A phosphoT288 levels were seen ...
Inhibitors,Activator,Agonist,antagonist,API,Aurora,Metabolic Disease,VEGFR-PDGFR,Other Intermediate,Others,MOF Chemicals,,Active Biopharma Corp
...[T]he [M.D. Anderson Cancer Center & Baylor College of Medicine] researchers concluded that [Aurora kinase] AK inhibition [produced by MK-0457] significantly reduces ovarian cancer tumor burden and cell proliferation, and increases tumor cell apoptosis in preclinical ovarian cancer mouse models. The researchers noted that the role of Aurora kinase inhibition in ovarian cancer merits further…
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Its important to ask about the experience of your local Aurora lawn care companys employees before you select the company for your job. Experienced lawn care experts know which species and types of grass, shrubs and plants work best in the Aurora climate, and know how to maintain them. CVSHome.com researches local pros and partners with the ones that consistently provide the highest quality of service, and also offer competitive pricing. When you hire someone to perform lawn maintenance in Aurora, make sure that you get multiple bids, and ask for references. Even a small difference in pricing can add up over the long run, especially if you are getting frequent Aurora lawn cutting service.. ...
We present an analysis of flickering (2-10 Hz) auroras observed with a state-of-the-art multispectral imaging system, Auroral Structure and Kinetics, located in Tromso, Norway. Short (1-2 s) periods of flickering aurora have been identified in which the frequency of the brightness oscillations decreases or increases smoothly over time. To the authors knowledge this is the first detailed analysis of such chirps in flickering aurora or field-aligned bursts. We have found that the electron precipitation energy is strongly anticorrelated with the flickering frequency during all identified chirps. This result is consistent with the theory that flickering aurora is caused by the resonance interaction between electromagnetic ion cyclotron waves and precipitating electrons and that the wave parallel phase velocity is the primary factor determining the electron acceleration produced by this mechanism. Other current theories known to the authors cannot completely explain our observations.. ...
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The Aurora (Ipl1)-related kinases are universal regulators of mitosis. We now show that Aurora-A, in addition to Aurora-B, regulates kinetochore function in human cells. A two-hybrid screen identified the kinetochore component CENP-A as a protein that interacts with Aurora-A. Aurora-A phosphorylated …
References for Abcams Recombinant Human Aurora A protein (ab86846). Please let us know if you have used this product in your publication
AMG 900 is a potent and selective, orally available small molecule aurora kinase inhibitor. Buy Aurora Kinase inhibitor AMG 900 from AbMole BioScience.
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.
ZM447439 does not prevent localization of Aurora B to centromeres. Immunofluorescence images of prometaphase DLD-1 cells stained to detect Aurora B (green), Sur
10 Feb 2016. In one of the first efforts to date to apply nanotechnology to targeted cancer therapeutics, researchers have created a nanoparticle formulation of a cancer drug that is both effective and nontoxic -- qualities harder to achieve with the free drug.. Their nanoparticle creation releases the potent but toxic targeted cancer drug directly to tumours, while sparing healthy tissue.. The findings in rodents with human tumours have helped launch clinical trials of the nanoparticle-encapsulated version of the drug, which are currently underway.. Aurora kinase inhibitors are molecularly targeted agents that disrupt cancers cell cycle.. While effective, the inhibitors have proven highly toxic to patients and have stalled in late-stage trials.. Development of several other targeted cancer drugs has been abandoned because of unacceptable toxicity.. To improve drug safety and efficacy, Susan Ashton and colleagues designed polymeric nanoparticles called Accurins to deliver an Aurora kinase B ...
SUMMARY: The experimental hepatitis C virus (HCV) polymerase inhibitor VX-222, being developed by Vertex, was generally well-tolerated and exhibited good antiviral activity over 3 days across a range o...
TY - JOUR. T1 - Aurora B-INCENP localization at centromeres/inner kinetochores is required for chromosome bi-orientation in budding yeast. AU - García-Rodríguez, Luis J.. AU - Kasciukovic, Taciana. AU - Denninger, Viola. AU - Tanaka, Tomoyuki. N1 - Funding: ERC (322682) and Wellcome Trust (096535/Z/11/Z).. PY - 2019/5/6. Y1 - 2019/5/6. N2 - For proper chromosome segregation in mitosis, sister kinetochores must interact with microtubules from opposite spindle poles (chromosome bi-orientation) [1, 2]. To promote bi-orientation, Aurora B kinase disrupts aberrant kinetochore-microtubule interactions [3-6]. It has long been debated how Aurora B halts this action when bi-orientation is established and tension is applied across sister kinetochores. A popular explanation for it is that, upon bi-orientation, sister kinetochores are pulled in opposite directions, stretching the outer kinetochores [7, 8] and moving Aurora B substrates away from Aurora-B-localizing sites at centromeres (spatial separation ...
PURPOSE: Despite over 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluate the role of Aurora A, identified as an upregulated candidate molecule in bladder cancer, in regulating bladder tumor growth. EXPERIMENTAL DESIGN: Gene expression in human bladder cancer samples was evaluated using RNA microarray and reverse-transcriptase PCR. The specific Aurora kinase A inhibitor MLN8237 (Millennium) was used to determine effects on bladder cancer cell growth using in vitro and in vivo models using malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells. RESULTS: Urothelial carcinoma upregulates a set of 13 mitotic spindle associated transcripts, as compared to normal urothelium, including MAD2L1 (7.6-fold), BUB1B (8.8-fold), Aurora kinases A (5.6-fold) and Aurora kinase B (6.2-fold). Application of MLN8237 (10nM-1µM) to the human bladder tumor cell lines T24 and UM-UC-3 induced dose
Accurate segregation of chromosomes in mitosis requires that spindle microtubules attach sister kinetochores to opposite poles of the mitotic spindle (biorientation). To achieve biorientation of all chromosomes, incorrect attachments are selectively destabilized, providing a fresh opportunity to biorient, whereas correct attachments are stabilized. Tension across the centromere may be the signal that distinguishes different attachment states, as spindle microtubules pull bioriented sister kinetochores in the opposite direction. Destabilization of incorrect attachments requires the Ipl1/Aurora B kinase, which phosphorylates kinetochore substrates that directly interact with microtubules. The present review focuses on how Aurora B regulates attachments in response to centromere tension.. ...
T he carcinogenic risk induced by low doses of ionizing radiation is controversial. It cannot be assessed with epidemiologic methods alone because at low. doses the data are imprecise and often conflicting. Since the 1970s, the radiation protection community has estimated the risk of low doses by means of extrapolation from the risk assessed at high doses, generally by using the linear no-threshold (LNT) model.. The LNT relationship implies P5091 molecular weight proportionality between dose and cancer risk. This approach is based on one set of data and two hypotheses: (a) The relationship between. dose and DNA damage in vivo seems linear from 1 mGy to 100 Gy with use of H2AX foci as a marker for DNA double-strand breaks (DSBs)-however, this marker is not specific (1); (b) each DSB is hypothesized to have the same probability of inducing cell transformation, irrespective of the Sapanisertib quantity of DSBs present simultaneously in the cell; and (c) each transformed cell is hypothesized ...
Hesperadin is an inhibitor of human Aurora B, which can prevent the phosphorylation of substrate with IC(50) of 40 nM. Growth of cultured bloodstream forms was also sensitive to Hesperadin (IC(50) of 50 nM). Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Consequently, growth arrested cells accumulated multiple kinetoplasts, flagella and nucleoli, similar to the effects of RNAi-dependent knockdown of TbAUK1 in cultured bloodstream forms cells. Molecular models predicted high-affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Collectively, these data demonstrate that cell cycle progression is essential for infections with T. brucei and that parasite Aurora kinases can be targeted with small-molecule inhibitors..............
The mitotic spindle is a highly specialized macromolecular machinery that ensures equal segregation of genetic information between daughter cells during mitosis. The assembly and operation of this complex and very dynamic structure have to be appropriately regulated to avoid generation of aneuploid cells. Numerous signaling molecules participate in this regulation, and they include the Aurora A kinase. Some of the functions of the Aurora A kinase during mitotic spindle assembly are now well established; they operate in G2 when the kinase is recruited to centrosomes. Aurora A participates in centrosome maturation by recruiting NDLE1 (Mori et al., 2007) and TACC3 (Kinoshita et al., 2005). In prometaphase, Aurora A participates in regulation of microtubule dynamics by contributing to the recruitment of factors involved in the dynamic instability of microtubules, including DDA3 (Jang and Fang, 2011), MCAK (Zhang et al., 2008), ch-TOG (De Luca et al., 2008; Asteriti et al., 2011), and KIF2A (Jang et ...
Aurora A kinase is overexpressed in aggressive lymphomas and may correlate with more histologically aggressive forms of disease. In a phase II study reported in Journal of Clinical Oncology, Jonathan W. Friedberg, MD, of University of Rochester Wilmot Cancer Center, and colleagues assessed the effects of the selective AAK inhibitor alisertib in patients with relapsed and refractory aggressive non-Hodgkin lymphoma (NHL). They found that the agent was generally well tolerated and exhibited activity that warrants further study.. Study Details. In the study, 48 patients with relapsed or refractory diffuse large B-cell lymphoma (n = 21), mantle cell lymphoma (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), or Burkitts lymphoma (n = 1) were treated with oral alisertib at 50 mg twice daily for 7 days in 21-day cycles. Patients had a median age of 67.5 years, 27% were female, 98% were white, 87% had Eastern Cooperative Oncology Group performance status of 0 or 1, ...
Aurora C kinase is an essential regulator of cytokinesis seeing that it stabilizes the intercellular channel within the midbody to ensure proper chromosomal segregation during cell department. tetraploidy, mitotic criminal arrest, and apoptosis of tumorigenic cells and inhibiting tumor formation in athymic naked rodents profoundly. These findings suggest molecular interaction between Aurora C and calmodulin in telophase and recommend that calmodulin serves as a gate sensor for chromosomal segregation PF-03814735 mistakes during mitosis. rodents/group with medication focus at 2 Meters (low), 10 Meters (moderate) and 40 Meters (high) in the consuming … Debate Lately, Steigemann et al. suggested an elegant model by which Aurora C is normally the essential regulator of abscission time, which responds to chromosome connection development by slowing down abscission to stabilize the intercellular channel until the chromosome connection is normally solved.12 In quality, a indication is provided by ...
TY - JOUR. T1 - Activation of Aurora-A Kinase by Protein Partner Binding and Phosphorylation Are Independent and Synergistic. AU - Dodson, Charlotte. AU - Bayliss, Richard. PY - 2012/1/6. Y1 - 2012/1/6. N2 - Protein kinases are activated by phosphorylation and by the binding of activator proteins. The interplay of these two factors is incompletely understood. We applied energetic analysis to this question and characterized the activation process of the serine/threonine kinase Aurora-A by phosphorylation and by its protein partner, targeting protein for Xenopus kinesin-like protein 2 (TPX2). We discovered that these two activators act synergistically and without a predefined order: each can individually increase the activity of Aurora-A, and the effect of both bound together is the exact sum of their individual contributions to catalysis. Unexpectedly, the unphosphorylated enzyme has catalytic activity that is increased 15-fold by the binding of TPX2 alone. The energetic contribution of ...
Lieutenant-Governor John Graves Simcoe gave the order for Yonge Street to be extended to Holland Landing in 1793, the first step toward the establishment of a community where Aurora now stands. Yonge Street opened between 1794 and 1796. In 1795, the first house in Aurora was built at Yonge St and Catherine Av.[5] The government began granting deeds to land in 1797. By 1801 there were fourteen homes.[6]. In 1804, Richard Machell became the first merchant at the crossroads of Yonge and Wellington and the hamlet soon became known as Machells Corners. Charles Doan was another early businessman at Machells Corners and became the first postmaster and later the first reeve. The post office was originally known as Whitchurch.[7]:10 As postmaster, he was influential in renaming the village Aurora, after the goddess Aurora from Roman mythology.[7]:10[a] Machell proposed to rename the town Match-Ville, ostensibly for the match factory in the town, but the name Aurora was more popular and ultimately ...
Aurora Seriate Calcio or simply Aurora Seriate was an Italian association football club, based in Seriate, Lombardy. Aurora Seriate last played in Serie D. The club was founded in 1967 and developed in the next decade within the parish dispute for several years provincial championships. In 2008, it won the championship of Prima Categoria and a historic promotion to Promozione. In the 2008-09 season in the Promozione, Aurora Seriate ended in fifth place but, due to winning the Italian Cup final category, the jump to 2009-10 Eccellenza was allowed. In Eccellenza, the first year ended in second place, behind Rudianese and losing the final of the playoffs by the later promoted Sterilgarda Castiglione. In 2010-11 Eccellenza, it won the championship and the promotion to 2011-12 Serie D. Aurora Seriate officially merged with fellow Lombardy and Serie D side FC AlzanoCene on 31 May 2015 to become Virtus Bergamo Alzano Seriate 1909. The teams colors were red and blue. Archived copy. Archived from the ...
Mller (Reviews, 27 Oct 2006, p. yielding monopolar spindles or bipolar spindles missing centrosomes, in keeping with earlier observations (7,8). Therefore delays mitotic development inside a SAC-dependent way. The simplest description for SAC activation is usually that inhibition of -TuRC induces spindle problems that prevent kinetochores from attaining complete MT occupancy and/or arriving under tension. Nevertheless, the writers argue that simple explanation isnt sufficient to describe their observations, saying that -TuRCCdeficient cells display abundant microtubule arrays with amphitelic-like chromosome micro-tubule connection. Rather, they hypothesize that -tubulin is usually a part of a signaling complicated that creates the SAC when -TuRC protein are abrogated. SAC activation in -TuRCCdeficient cells argues against the hypothesis that -tubulin can be an activator from the SAC, although inside a formal feeling, -TuRC proteins become negative regulators from the SAC, as will additionally ...
Myc oncogenes encode transcription factors that bind to E-box sequences in DNA, driving the expression of a large number of target genes and are deregulated in approximately 70% of human cancers. Deregulated Myc expression cause enhanced proliferation (which is counteracted by apoptosis), angiogenesis and cancer. Though Mycs importance in induction of S phase has been established, less is known about its functions in the G2 and M phases of the cell cycle. Paper I addresses the targeting of the Myc targets Aurora kinase A and B that have roles in G2/M transition and provide evidence that pharmaceutical Aurora kinase inhibition causes cell cycle arrest and apoptosis in a Myc-selective manner and is useful in treating Myc-induced lymphomas in vivo.. The assumption that the important target genes responsible for the biological effects of Myc overexpression were those encoding components of the cell cycle machinery lead to little interest in other potentially important groups of target genes. ...
Supplementary MaterialsSupplementary material 1 (AVI 412 kb) 13238_2017_407_MOESM1_ESM. regulators of mitosis. Aurora kinase B (AurkB) is usually ubiquitously expressed while Aurora kinase C (AurkC) is usually specifically expressed in gametes and preimplantation embryos. Decitabine price We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level experienced the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and ...
The second query is aimed to identify proteins overexpressed in cancer as compared with its normal cellular counterpart. Based on the list of candidate cancer proteins identified by Polanski and Anderson (22), a search was made to investigate whether any proteins on this list were expressed at high levels in at least six of 12 colorectal cancer patients, whereas the expression in normal glandular cells in the colon is low (Fig. 4B). Again four proteins fit these criteria. The first protein is the serine/threonine-protein kinase 12 (Aurora-B), also known as Aurora-related kinase 2. The Aurora kinases associate with microtubules during chromosome movement and segregation, and this protein localizes to microtubules near kinetochores, specifically to the specialized microtubules called K-fibers. The tissue profiles of the Human Protein Atlas show strong expression in six of 12 colon cancers, and the expression is, as expected, in the nuclei. The protein is also expressed highly in a subset of lung ...
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Neutralizing antibodies often identify parts of viral envelope glycoproteins that are likely involved in receptor binding or various other areas of virus entry. pathogen entry. The entrance of individual immunodeficiency pathogen type 1 (HIV-1) in to the web host cell is certainly mediated with the viral envelope glycoproteins. The HIV-1 envelope glycoproteins derive from NVP-AEW541 a approximately 850-residue precursor thats intensely glycosylated and eventually cleaved in to the older gp120 and gp41 subunits (72). The envelope glycoprotein spike on HIV-1 virions features being a homotrimer formulated with three gp120 outdoor envelope glycoproteins and three gp41 transmembrane envelope glycoproteins (14, 72). The HIV-1 gp41 glycoprotein is certainly a sort I membrane proteins, and its own ectodomain interacts noncovalently with gp120 to wthhold the latter in the virion surface area (19, 45). The gp120 glycoprotein comprises a lot of the open surface area from the envelope glycoprotein ...
Aurora Trout are distinguished from other Brook Trout mainly in terms of skin colouration: (1) adult Aurora Trout lack the yellow spots and vermiculations that typically occur on the dorsal surface of other Brook Trout; and (2) the numerous red spots surrounded by blue halos characteristically found on the sides of Brook Trout are greatly reduced in number or are absent on Aurora Trout
The basic helix-loop-helix transcription factor, Id1, was shown to induce tetraploidy in telomerase-immortalized nasopharyngeal epithelial cells in this study. Using both transient and stable Id1-expressing cell models, multiple mitotic aberrations were detected, including centrosome amplification, binucleation, spindle defects, and microtubule perturbation. Many of these abnormal phenotypes have previously been reported in cells overexpressing Aurora A. Further experiments showed that Id1 could stabilize Aurora A, whereas knocking down Aurora A expression in Id1-expressing cells could rescue some of the mitotic defects. The mechanisms by which Aurora A could be modulated by Id1 were explored. DNA amplification of the Aurora A locus was not involved. Id1 could only weakly activate the transcriptional activity of the Aurora A promoter. We found that Id1 overexpression could affect Aurora A degradation, leading to its stabilization. Aurora A is normally degraded from mitosis exit by the APC/C(Cdh1)
Key cells divide asymmetrically during the development of multicellular organisms to give rise to offspring with different fates. In the Drosophila external sensory organ, asymmetrical division depends on polarization of the precursor cells during interphase and the consequent unequal distribution during mitosis of the protein Numb, which determines cell fate. Gonzalez discusses recent research implicating the mitotic kinase Aurora-A in the asymmetric localization of Numb in sensory organ pI precursor cells, a new function that appears to be independent of Aurora-As known roles in regulating centrosomal maturation and the organization of mitotic spindle microtubules.. ...
03); **represents significant difference between. group 1%FBS + 10 ng/ml TGF-β1′ and group 1%FBS (P = 0.044). Figure 6 The effects of TGF-β1 on expression levels of PKCα and p38 MAPK. BxPC3 cells were treated with 0.1, 1 and 10 ng/ml TGF-β1 for 10 min, 30 min and 24 h. Total cellular protein was extracted and subjected to western blotting analysis to detect expression of PKCα, phosphorylated-p38/total p38 MAPK and phosphorylated-ERK1/2/total ERK1/2. Bx represents BxPC3 cells and Bx/T represents the stably transfected BxPC3 cells with TGF-β1 plasmid. To determine whether the induced PKCα activity is responsible for the TGF-β1-induced decrease in the sensitivity of BxPC3 cells to cisplatin, we treated the cells with a selective PKCα inhibitor, Gö6976, and assessed TGF-β1-induced drug resistance. We found that inhibition of PKCα. activity could partially reverse TGF-β1-induced drug resistance of BxPC3 cells to cisplatin PLX4032 in vivo (Figure 7). Figure 7 MTT assay. (A) BxPC3 ...
https://www.aurora-clinics.co.uk/news/pip-breast-implants-news-flash/ Visit the Aurora Clinics website for the latest news on PIP breast implants. This surgery information video is all about PIPs and what the rate of rupture is within them. The statistics at the disposal of Aurora only refers to the patients Aurora has treated with PIP implants. This statistic could well be higher […]. ...
International is a privately-held company, owned primarily by the Aurora Capital Group. Aurora Capital is a Los Angeles-based investment firm formed in 1991 that acquires and builds companies in partnership with operating management. The firm currently manages approximately $2 billion in capital and is committed to investing in companies with unique, defensible market positions. Aurora is dedicated to generating long-term value principally through investing the time and resources necessary to enhance the fundamentals of each of its businesses. . As information the algorithmic processes have been questioned and challenged here to claiming short payments with Ingenix with Safeco. This sounds like many of the law suits in court for the short pay on the out of network healthcare claims in theory. ...
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We describe a novel clinical phenotype associating T- and B-cell lymphopenia intermittent neutropenia and atrial septal flaws in 3 associates of the consanguineous kindred. with the STK4 ortholog DAF16 protects against cell loss of life induced by oxidative tension. Furthermore when DAF16 cannot perform the phosphorylation function living from the worms is normally measurably decreased. 19 Surprisingly Stk4-deficient mice experienced progressive loss of B and T cells because of excessive apoptosis. 20-22 STK4 could also possess a protective function maintaining cellular viability Thus. STK4 phosphorylates transcription elements within the FOXO family members including FOXO3 and FOXO1 within a stress-response pathway.19 21 STK4 participates in a number of other pathways. Binding of RASSF1A and NORE1A to STK4 homodimers inhibits STK4 kinase activity.20 23 Binding of RAPL to STK4 is vital for lymphocytes to polarize and adhere24 and potentially to regulate proper egress from thymus.22 Our ...
Background The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the merchandise from the t(2;5)chromosomal translocation within non-Hodgkins lymphoma. CNS by evaluation. However, furthermore to Mizolastine supplier appearance of DAlk in the mind, careful evaluation reveals anadditional early function for DAlk within the developing visceralmesoderm where its appearance is certainly coincident withactivated ERK. Bottom line Within this paper a Alk is described Mizolastine supplier by all of us RTK that is expressed within the developing embryonic mesoderm and CNS. Our data offer proof for the everyday living of a DAlk RTK pathway in hybridization research have uncovered ALK appearance within the developing anxious program and ALK happens to be a book orphan receptor tyrosine kinase thats suspected to try out important function in the standard advancement and function from the anxious system. Within this paper a homologue is certainly ...
The critical role of NIK in regulating non-canonical and canonical NF-κB pathways in MM,4-6 together with the fact that NIK and Aurora kinases can converge on common targets,24-26 prompted us to hypothesize that NIK might interfere with and reduce or bypass the NF-κB inhibitory effects exerted by pan-AKI on MM cells. In support of this hypothesis, we found that pan-AKI induce NIK protein stabilization and that this depended on the downregulation of the TRAF2 protein, one of the critical NF-κB negative regulators that, together with TRAF3, form a molecular bridge that couples NIK to the NIK K48-ubiquitin ligase cIAP1/2.6,7 We also found that TRAF2 reduction was sufficient to elevate NIK protein levels in MM cells harboring alterations in the TRAF3-binding domain of NIK or in TRAF3 itself, thus confirming that TRAF2 can regulate NIK stabilization independent of TRAF3.4,45. Although experimental overexpression of NIK led to a marked activation of both NF-κB and STAT3 pathways, its induction by ...
... strong interest has shifted towards the aurora kinase proteins. The kinase gene Aurora A when amplified acts as an oncogene ... The localization of MAD2 and BubR1 to the kinetochore may also be dependent on the Aurora B kinase. Cells lacking Aurora B fail ... Aurora-B/Ipl1 kinase of the chromosomal passenger complex functions as the tensions sensor in improper kinetochore attachments ... The Aurora-B/Ipl1 kinase is also critical in correcting merotelic attachments, where one kinetochore is simultaneously attached ...
Aurora kinase has two forms which are designated Aurora kinase A and Aurora kinase B. These proteins play a key role in mitosis ... In some human cancers, the expression and kinase activity of Aurora kinases have been up-regulated and has been looked into as ... A possible causes of multipolar spindle formation involve regulation of protein kinase family known as Aurora kinase. ... Jingyan Fu, Fu (26 January 2007). "Roles of Aurora Kinases in Mitosis and Tumorigenesis". Molecular Cancer Research. 5 (1): 1- ...
"Cyclin Dependent Kinase (CDK) and Aurora Kinase (AK) inhibitors , Cyclacel R&D for anticancer drugs acting on cell cycle". www. ...
Aurora kinases are required for proper spindle assembly and separation. Aurora A associates with centrosomes and is believed to ... Spindle assembly is largely regulated by phosphorylation events catalyzed by mitotic kinases. Cyclin dependent kinase complexes ... with many of these proteins serving as Aurora and Polo-like kinase substrates. In a properly formed mitotic spindle, bi- ... Polo-like kinase, also known as PLK, especially PLK1 has important roles in the spindle maintenance by regulating microtubule ...
"Arabidopsis α Aurora Kinases Function in Formative Cell Division Plane Orientation". The Plant Cell. 23 (11): 4013-4024. doi: ... Another midline-localized protein, "two-in-on" (TIO), is a putative kinase and is also required for cytokinesis as shown by ... "Microtubule-Associated Kinase-like Protein RUNKEL Needed for Cell Plate Expansion in Arabidopsis Cytokinesis". Current Biology ... Oh, Sung Aeong; Bourdon, Valérie; Dickinson, Hugh G.; Twell, David; Park, Soon Ki (2014-03-01). "Arabidopsis Fused kinase TWO- ...
"Drugging MYCN through an Allosteric Transition in Aurora Kinase A". Cancer Cell. 26: 414-27. doi:10.1016/j.ccr.2014.07.015. PMC ... N-Myc is also stabilized by aurora A which protects it from degradation. Drugs that target this interaction are under ... development, and are designed to change the conformation of aurora A. Conformational change in Aurora A leads to release of N- ... "Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma". Cancer Cell. 15 (1): 67-78. doi:10.1016/j. ...
2002). "Human TPX2 is required for targeting Aurora-A kinase to the spindle". J. Cell Biol. 158 (4): 617-23. doi:10.1083/jcb. ... TPX2 has been shown to interact with Aurora A kinase , KIF15, and Ran. GRCh38: Ensembl release 89: ENSG00000088325 - Ensembl, ... "Human TPX2 is required for targeting Aurora-A kinase to the spindle". J. Cell Biol. United States. 158 (4): 617-23. doi:10.1083 ... Bayliss R, Sardon T, Vernos I, Conti E (2003). "Structural basis of Aurora-A activation by TPX2 at the mitotic spindle". Mol. ...
Other kinases that have interested Sebti include Rho-associated kinase and Aurora kinase. STAT3. In 2003 the Sebti lab ... May 30, 2014). "Dual Aurora A and JAK2 kinase blockade effectively suppresses malignant transformation". Oncotarget. 5 (10): ... Kinases. Sebti's work on the kinase Akt led to his interest in Triciribine. ... October 1, 2012). "RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor ...
Stabilization of DGL7 in cell occurs due to phosphorylation by Aurora A kinase. Expression of DGL7 is found in cancer and stem ... 2005). "Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A". Mol. ... Yu CT, Hsu JM, Lee YC, Tsou AP, Chou CK, Huang CY (July 2005). "Phosphorylation and stabilization of HURP by Aurora-A: ... implication of HURP as a transforming target of Aurora-A". Mol. Cell. Biol. 25 (14): 5789-800. doi:10.1128/MCB.25.14.5789- ...
2006). "Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma". Int. J. Cancer. 118 (2): 357-63. doi:10.1002/ ... "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 ...
... has been shown to interact with INCENP, Survivin and Aurora B kinase. GRCh38: Ensembl release 89: ENSG00000134690 - ... "Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung ...
... (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. It was investigated as a ... a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas". Journal of ...
The problem with K562 cells, and many other cancer cell types, is an overabundance of Aurora kinases. These kinases play a role ... However, the overabundance of Aurora kinases allows for uncontrolled cellular division, resulting in cancer. Inhibiting these ... This gene targets the cyclin-dependent kinase inhibitor, p21, and causes cell differentiation, cell cycle arrest in G1, and ...
2005). "Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells ... Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP ... "Entrez Gene: AURKC aurora kinase C". Human AURKC genome location and AURKC gene details page in the UCSC Genome Browser. ... This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal ...
"NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of ... Interaction of NEDD9 with Aurora A kinase may also play a role in tumor invasion. NEDD9 binds to and regulates acetylation of ... NEDD9 binds directly to the Aurora-A mitotic kinase at the centrosome, and promotes its activity, allowing cells to enter ... Other phosphorylation events in this region are imposed by the kinase Aurora-A, which phosphorylates residue S296, for ...
Disassembly of cilia requires the action of the Aurora A kinase . Exceptions where IFT is not present include Plasmodium ... Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (June 2007). "HEF1-dependent Aurora A activation induces ...
2006). "The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A". Mol. Cell. 20 (2): 237-49. doi:10.1016 ...
The CAS family member NEDD9 has also been shown to interact directly with AURKA (encoding Aurora-A kinase) to regulate cell ... it is possible that CASS4 may similarly interact with aurora-A kinase. CASS4 signaling may contribute to platelet activation ... "The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome". Nature ... These include association with FAK and Src family kinases at focal adhesions to transmit integrin-initiated signals to ...
"Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research. 26 (5A): 3585-93 ...
"Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model". ... Chen Y, Riley DJ, Zheng L, Chen PL, Lee WH (Dec 2002). "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is ... Chen Y, Riley DJ, Zheng L, Chen PL, Lee WH (Dec 2002). "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is ... and drug sensitivity are preferentially regulated by anti-HER2 antibody through phosphatidylinositol 3-kinase-AKT signaling". ...
BI811283 is a small molecule inhibitor of the aurora B kinase protein being developed by Boehringer Ingelheim for use as an ... a novel inhibitor of Aurora B kinase, on tumor senescence and apoptosis". J. Clin. Oncol. 28 (15 Suppl e13632). Rein DT, ... Sutendra, G; Michelakis, ED (2013). "Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology". Frontiers in ... studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage. ...
"Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells". J. Biol. Chem. 278 (1): 486-90. doi:10.1074/ ... Survivin has been shown to interact with: Aurora B kinase, CDCA8, Caspase 3, Caspase 7, Diablo homolog and INCENP. GRCh38: ...
... phosphorylation and compartmentalization is regulated by Aurora A and Aurora B pathways. Other kinases have been reported ... Inhibition of Aurora B kinase by specific small molecule drugs resulted in the release of JADE1S-mediated cytokinetic delay and ... Six amino acid residues were identified to be phosphorylated in cell cycle-dependent manner via Aurora A kinase pathway. JADE1 ... Since Aurora B is a key regulator of the NoCut, JADE1S is likely to regulate cytokinesis at the abscission checkpoint control. ...
Plays an important role in regulation of the kinase activity of AURKA/Aurora-A for mitotic commitment. JUB (gene) has been ... Hirota T, Kunitoku N, Sasayama T, Marumoto T, Zhang D, Nitta M, Hatakeyama K, Saya H (2003). "Aurora-A and an interacting ... Augments Mitogen-Activated Protein Kinase Activity in Fibroblasts, and Promotes Meiotic Maturation of Xenopus Oocytes in a Grb2 ... Protein Ajuba Influences Interleukin-1-Induced NF-κB Activation by Affecting the Assembly and Activity of the Protein Kinase Cζ ...
Zeitlin SG, Shelby RD, Sullivan KF (2002). "CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in ... "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore ...
Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP ... The ARK binding region has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has ... Leverson JD, Huang HK, Forsburg SL, Hunter T (April 2002). "The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts ... and aurora-B kinase during male mouse meiosis". J. Cell Sci. 116 (Pt 6): 961-74. doi:10.1242/jcs.00330. PMID 12584241. ...
... a new interaction partner for human serine/threonine kinase aurora-B". Biochemical and Biophysical Research Communications. 336 ...
2004). "Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model". ... "Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1". Chromosoma. 113 (1): 1-15. ...
"Phosphorylation of HsMis13 by Aurora B kinase is essential for assembly of functional kinetochore". J. Biol. Chem. 283 (39): ...
... has been shown to interact with: Aurora A kinase, CD29 NME3, Protein SET, RAR-related orphan receptor alpha, RAR-related ... "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1". Nucleic Acids Res. 30 (24): 5465-75 ... Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene. It is thought to be a metastasis ... Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) ...
The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... 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/ ... "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase". Cell. 113 (4): 507-17. doi:10.1016/ ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... 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 ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Montgomery, K. & Mak, A.S. (1984). „In vitro phosphorylation of tropomyosin by a kinase from chicken embryo". J. Biol. Chem. ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... deBelle, I. & Mak, A.S. (1987). „Isolation and characterization of tropomyosin kinase from chicken embryo". Biochim. Biophys. ...
Aurora at Jupiter's north pole as seen in ultraviolet light by the Hubble Space Telescope. ... B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase ...
"Frequent alterations in the expression of serine/threonine kinases in human cancers". Cancer Research 66 (16): 8147-54. PMID ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ...
"BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition". J. Biol. Chem. 279 (19): 19643-8. doi:10.1074/jbc. ... 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 ...
1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ... "Entrez Gene: CIT citron (rho-interacting, serine/threonine kinase 21)".. *^ a b c Madaule P, Furuyashiki T, Reid T, Ishizaki T ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... The complex also contains 2 regulatory enzymes, a kinase and a phosphorylase. The BCKDHA gene encodes the alpha subunit of E1, ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3». ... full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2». Cancer Res. 69 (3 ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... O'Brien, K A; Lemke S J, Cocke K S, Rao R N, Beckmann R P (1999). «Casein kinase 2 binds to and phosphorylates BRCA1». Biochem ...
"Protein kinase C and lipid signaling for sustained cellular responses" (ABSTRACT). FASEB J. 9 (7): 484-96. PMID 7737456 ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... "The extended protein kinase C superfamily". Biochem. J. 332 ( Pt 2): 281-92. PMC 1219479. PMID 9601053 ...
Soderling TR (1999). „The Ca-calmodulin-dependent protein kinase cascade". Trends in Biochemical Sciences. 24 (6): 232-6. PMID ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... Lisman, J. E. (1985) A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase. ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... kinase activity. • protein binding. • ATP binding. • protein serine/threonine kinase activity. • protein kinase activity. ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • protein serine/threonine kinase activity. • protein binding. • ATP binding. • magnesium ion binding ... Microtubule-associated serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MAST1 gene.[5] ...
Dhillon AS, Kolch W (2002). "Untying the regulation of the Raf-1 kinase". Arch. Biochem. Biophys. 404 (1): 3-9. PMID 12127063. ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... Li P, Wood K, Mamon H, Haser W, Roberts T (February 1991). "Raf-1: a kinase currently without a cause but not lacking in ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase binding. • protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ... kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ...
Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical ... "Casein Kinase II (CK2) as a Therapeutic Target for Hematological Malignancies". Current Pharmaceutical Design. 23 (1): 95-107. ... kinase (PI3K)/AKT axis, Hedgehog signaling pathway, nuclear factor-kappaB and Activating Transcription Factor 2 have also been ... is a potent TGF-β type I receptor kinase inhibitor that was demonstrated to reduce the size, the growth rate of tumors, and the ...
For example, phosphorylation of Serine 194 on RalA by the kinase Aurora A results in the relocation of RalA to the inner ... whereas phosphorylation of Serine 198 on RalB by the kinase PKC results in the relocation of RalB to other internal membranes ...
... it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting ... Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, Boehlecke B, Chesson AL Jr, Friedman L, Maganti R, Owens J, ... Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its ... calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5.. Figure 2 ...
December 2012). "Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence after chemotherapy in patient- ... Utilizing PDX triple negative breast cancer models, scientists found that aurora kinase inhibitors slows tumor growth rate and ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ... This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide ...
Aurora at Jupiter's north pole as seen in ultraviolet light by the Hubble Space Telescope. ... B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein serine/threonine kinase activity. • ATP binding. • kinase activity. • protein binding. Cellular component. • cell ... Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.[5][6][7] ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids 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 ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... kinase activity. • protein binding. • RNA polymerase II carboxy-terminal domain kinase activity. • ATP binding. • protein ... Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.[5][6] ...
... full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Research. 69 ... kinase binding. • RNA binding. • protein heterodimerization activity. • ubiquitin-protein transferase activity. • protein ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... A major target of Akt kinases is glycogen synthase kinase-3. EC 2.7.1.37 Pelle. is a serine/threonine kinase that can ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... A serine/threonine protein kinase (EC 2.7.11.1) is a kinase enzyme that phosphorylates the OH group of serine or threonine ( ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein kinase activity. • cAMP-dependent protein kinase activity. • ADP binding. • AMP-activated protein kinase activity. • ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... cAMP-dependent protein kinase regulator activity. • protein kinase binding. • ATP binding. • adenyl ribonucleotide binding. ...
The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging ... Aurora kinases: shining lights on the therapeutic horizon? Oncogene. 2005 Jul 28;24(32):5005-15. doi: 10.1038/sj.onc.1208752. ... The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging ... This review details new developments in the field and analyses the potential of Aurora kinases as anticancer targets. ...
Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. FEBS Lett 2005;579:3385-91. ... Aurora-C kinase is a novel chromosomal passenger protein that can complement aurora-B kinase function in mitotic cells. Cell ... Aurora Kinases. The aurora family comprises three related kinases that share the highest degree of sequence homology in their ... that aurora kinases are appropriate drug targets; and that inhibitors of these particular aurora kinases can add to the cancer ...
Hesperadin is a human Aurora B inhibitor with an IC50 of 40 nM for the prevention of the phosphorylation of substrate. Find all ... The Aurora B kinase assay:. For the Aurora B kinase assay, HeLa cells are lysed in a buffer containing 50 mM NaCl. The whole ... less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. Phase 2. ... Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, ...
Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors. The safety and scientific validity ... Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase ... Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors. ... Pharmacokinetic And Pharmacodynamic Trial Of The Oral Single Agent Aurora Kinase Inhibitor PF-03814735 In Patients With ...
The Aurora family of serine/threonine kinases (Aurora A, Aurora B, and Aurora C) plays a key role in cells orderly progression ... SNS-314, a novel aminothiazole-derived urea, is a selective inhibitor of Aurora kinases A, B, and C with IC50 values in the low ... SNS-314, a potent inhibitor of Aurora kinases, has preclinical anti-tumor activity and induces apoptosis. Marc Evanchik, ... Heat Shock Protein Inhibitors, Aurora Kinase, and Other Mitotic Inhibitors: Poster Presentations - Proffered Abstracts. *. GF- ...
... an ATP-competitive dual inhibitor of MEK and Aurora kinases. Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 ... Inhibition of both MEK and Aurora kinase in KRAS-mutant tumors was observed when BI 847325 was administered once weekly at 70 ... Biomarker analysis suggested that this effect was primarily due to inhibition of MEK in BRAF-mutant models but of Aurora kinase ... Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases. Patrizia ...
The Aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Amir Faisal, ... The Aurora kinases regulate key stages of mitosis including centrosome maturation, spindle assembly, chromosome segregation and ... The Aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo ... The Aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo ...
Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates ... Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates ... Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates ... Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates ...
Metazoans contain three aurora-related kinases. Aurora A is required for spindle formation while aurora B is required for ... Less is known about the function of the aurora C kinase.. Consistent with its role in spindle formation, aurora A kinase ... In each system, aurora A kinase controls spindle formation while aurora B kinase regulates chromosome disjunction and ... pombe aurora-related kinase, which we will refer to as ark1+ (aurora-related kinase; SPCXC320.13C at Sanger centre; CAA18315 at ...
aurora kinase inhibitor III ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental ...
Results: We overexpressed GFP fused aurora B kinase in normal rat kidney epithelial cells. Using spinning disk confocal ... Abdullah, A.-S., Foong, C., Murata-Hori, M. (2005-11-09). Specific distribution of overexpressed aurora B kinase during ... Specific distribution of overexpressed aurora B kinase during interphase of normal epithelial cells. ... Myosin II regulatory light chain, one of the possible targets for aurora B, did not colocalize with cortical aurora B-GFP, ...
Aurora-A and -B expression and kinase activity is elevated in a variety of human cancers and is associated with high ... AMG 900 is a highly potent and selective pan-aurora kinase inhibitor that has entered clinical evaluation in adult patients ... a proximal substrate of aurora-B and inhibits the growth of multiple human tumor xenografts, including multidrug-resistant ... The Aurora family of serine-threonine kinases are essential regulators of cell division in mammalian cells. ...
Three Aurora kinases have been identified in mammalian cells to date, Aurora A, Aurora B, Aurora C. Besides being implicated as ... Aurora kinase helps the dividing cell dispense its genetic materials to its daughter cells. Defects in this segregation can ... mitotic regulators, these three kinases have generated significant interest in the cancer research field due to their elevated ... Aurora kinases are serine/threonine kinases that are essential for cell proliferation. ...
Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic ... A high-throughput small molecule screen identifies synergism between DNA methylation and Aurora kinase pathways for X ... Activation loop phosphorylation of a protein kinase is a molecular marker of organelle size that dynamically reports flagellar ...
As mentioned above, there are three classes of aurora kinases: Aurora A (a.k.a. Aurora 2) functions during prophase of mitosis ... Aurora kinases are serine/threonine kinases that are essential for cell proliferation. The enzyme helps the dividing cell ... Aurora inhibitor Bolanos-Garcia V M. Aurora kinases. The International Journal of Biochemistry & Cell Biology 37 (2005) 1572- ... Giet R, Prigent C. Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. Journal of Cell ...
The human genome contains three members the Aurora kinase family: Aurora A kinase, Aurora B kinase and Aurora C kinase. The ... Aurora A and Aurora B kinases play important roles in mitosis. The Aurora A kinase is associated with centrosome maturation and ... Aurora A phosphorylation directs the cytoplasmic polyadenylation translation of mRNAs, like the MAP kinase kinase kinase ... contain orthologues only to Aurora A and Aurora B. In all studied species, the three Aurora mitotic kinases localize to the ...
Aurora C is a member of mitotic serine/threonine kinases that regulate centrosome maturation, chromosome segregation, and ... Recombinant full-length human AURORA C was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. ... Use with ADP-Glo™ Kinase Assay. The ADP-Glo™ Kinase Assay is a luminescent kinase assay that measures ADP formed from a kinase ... The AURORA C Kinase Enzyme System can be purchased with or without the ADP-Glo™ Kinase Assay reagents. Used together, the ADP- ...
Aurora A belongs to a multigenic family of mitotic serine/threonine kinases, which are involved in the control of chromosome ... Recombinant full-length human Aurora A was expressed by baculovirus in Sf9 cells using an N-terminal GST tag. ... Aurora A NCBI Database Entry. The Aurora A Kinase Enzyme System can be purchased with or without the ADP-Glo™ Kinase Assay ... Use with ADP-Glo™ Kinase Assay. The ADP-Glo™ Kinase Assay is a luminescent kinase assay that measures ADP formed from a kinase ...
AURORA KINASE A. A. 287. Homo sapiens. Mutation(s): 0 Gene Names: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ... Sar156497, an Exquisitely Selective Inhibitor of Aurora Kinases.. Carry, J., Clerc, F., Minoux, H., Schio, L., Mauger, J., Nair ... The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and ... The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and ...
The kinases Aurora-A, -B and -C represent a family of s … ... Aurora-kinase inhibitors as anticancer agents Nat Rev Cancer. ... The kinases Aurora-A, -B and -C represent a family of such targets and several small-molecule inhibitors have been shown to ... What have these studies taught us about the therapeutic potential of inhibiting this family of kinases? ...
B kinase with putative anti-tumoral activity. Inhibitors of aurora kinases were shown to induce apoptosis in vitro and in vivo ... Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways.. Li M1, Jung A, Ganswindt U, Marini P, Friedl A ... ZM447439 (ZM) is a potent and selective inhibitor of aurora-A and - ...
Aurora kinase A. A. 282. Homo sapiens. Mutation(s): 1 Gene Names: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ... Functional Role of Conserved HxD-histidine in the Catalytic Core of Protein Kinase. Zhang, L., Wang, J., Hou, L., Cao, P., Wu, ...
... aurora kinase inhibitors as a promising therapeutic option in myeloma can be tailoredly given to patients expressing aurora-A, ... Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma.. Hose D1, Rème T, Meissner T, Moreaux J, ... A1) Inhibition of proliferation of 20 myeloma cell lines by the pan-Aurora-kinase inhibitor VX680 in graded concentrations vs. ... Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma ...
Aurora kinase B. Q96GD4. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. Pharmacological action?. ... Aurora kinase B. Kind. protein. Organism. Humans. Polypeptides. Name. UniProt ID. ...
Compare Aurora Kinase B ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and ... Aurora Kinase B ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for ... Your search returned 58 Aurora Kinase B ELISA ELISA Kit across 7 suppliers. ... Mouse/Human/Rat Phospho-AURKB / Aurora-B (Thr232) ELISA Kit (Cell-Based Phosphorylation ELISA) ...
MLN8054 inhibits recombinant Aurora A kinase activity in vitro and is selective for Aurora A over the family member Aurora B in ... B) IC50 values of MLN8054 against recombinant Aurora A, Aurora B, and a panel of other selected kinases. Kinase activity was ... Aurora A and Aurora B are structurally related serine/threonine protein kinases that function during mitosis. In humans, these ... The selectivity of MLN8054 for Aurora A over the structurally related Aurora B kinase was evaluated in HCT-116 tumor cells by ...
Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC). ... Tension sensing by Aurora B kinase is independent of survivin-based centromere localization Nature. 2013 May 2;497(7447):118-21 ... These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for ... Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC). ...
Aurora Kinases as Druggable Targets in Cancer Therapy » Blog Archives Menu Not Found. Skip to content *Home ...
... Demidov D., Van Damme D., ... Aurora-like kinases play key roles in chromosome segregation and cytokinesis in yeast, plant, and animal systems. Here, we ... which share high amino acid identities with the Ser/Thr kinase domain of yeast Ipl1 and animal Auroras. Structure and ... whereas the diversification of plant alpha and beta Aurora kinases predates the origin of land plants. The transcripts and ...
The effect of the clinical Aurora-kinase inhibitor VX680 on proliferation of 20 human-myeloma-cell-lines and survival of 5 ... We found Aurora-A and -B to be expressed at varying frequencies in primary myeloma-cells of different patient-cohorts, Aurora-C ... In conclusion, using gene expression profiling, Aurora-kinase inhibitors as promising therapeutic option for newly-diagnosed ... absent Aurora-A expression show a significantly higher proliferation rate, but neither a higher absolute number of chromosomal ...
Aurora Kinase B (Aurora 1 or Aurora And IPL1 Like Midbody Associated Protein 1 or Serine/Threonine Protein Kinase 12 or Serine/ ... Kinase B - Pipeline Review, H2 2018 drug pipelines has been added to ResearchAndMarkets.coms offering. ... Aurora Kinase B (Aurora 1 or Aurora And IPL1 Like Midbody Associated Protein 1 or Serine/Threonine Protein Kinase 12 or Serine/ ... Threonine Protein Kinase 5 or Serine/Threonine Protein Kinase Aurora B or STK1 or AURKB or EC 2.7.11.1) pipeline Target ...
Ausgesuchte Qualitäts-Hersteller für Aurora Kinase C Antikörper. Hier bestellen. ... Monoklonale und polyklonale Aurora Kinase C Antikörper für viele Methoden. ... aurora kinase C , ARK-3 , aurora 3 , aurora-related kinase 3 , aurora/IPL1-related kinase 3 , aurora/IPL1/EG2 protein 2 , ... serine/threonine-protein kinase aurora-C , aurora B , aurora/Ipl1/Eg2 protein 1 , serine/threonine kinase 13 (aurora/IPL-like) ...
The human aurora kinase family comprises three members: Aurora A, B and C (AURKA, AURKB and AURKC). Aurora A is important in ... Aurora kinases are a highly conserved family of enzymes which add phospho-groups to Serine/Threonine residues of substrate ... The involvement of these kinases in cell division and deregulated expression of aurora A and B in tumor cells (often resulting ... BioVision proudly offers several aurora kinase inhibitors including the ones mentioned above and more. ...
Aurora A (IC50 = 0.004 uM) over Aurora B (IC50 = 0.172 uM). Find all the information about MLN8054 for cell signaling research. ... Aurora Kinase Inhibitors with Unique Features. * Pan Aurora Kinase Inhibitors. Danusertib (PHA-739358) : Pan-Aurora kinase ... less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. Phase 2. ... Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, ...
Selected quality suppliers for anti-Aurora Kinase B antibodies. ... Order monoclonal and polyclonal Aurora Kinase B antibodies for ... aurora kinase B-Sv1 , aurora kinase B-Sv2 , aurora- and Ipl1-like midbody-associated protein 1 , aurora-1 , aurora-B , aurora- ... Serine/threonine-protein kinase aurora-B-B , aurora kinase B-B , aurora-B-B , aurora/IPL1-related kinase 2-B , serine/threonine ... serine/threonine kinase a , aurora kinase B , serine/threonine-protein kinase 12-like , Aurora/IPL1-related kinase 2-B , Serine ...
2008). Dictyostelium Aurora kinase has properties of both Aurora A and Aurora B kinases. Eukaryot. Cell 7: 894-905. ... 2010). A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells. J. Cell Sci. ... Aurora kinases function as key regulators of mitosis. Yeasts have a single Aurora kinase, whereas metazoans and land plants ... 2009). Aurora-C kinase supports mitotic progression in the absence of Aurora-B. Cell Cycle 8: 2984-2994. ...
Aurora kinase inhibition is a new mechanism of action. It helps to create the structure that separates chromosomes in cells, an ... Like most Aurora kinases, those compounds dont distinguish between the A and B forms. According to Niculescu, MLN8237s ... There are no approved Aurora kinases on the market; however, there are others in development, including AT9283 from Cancer ... Millennium Starts Pivotal Trial of Its Aurora Kinase Drug MLN8237 in PTCL ...
Aurora kinase A, Serine/threonine kinase 15, Aurora/IPL1-related kinase 1, Breast tumor-amplified kinase, Aurora-A, Aurora- ... AURKA (Aurora Kinase A) belongs to the mitotic serine/threonine kinases family. AURKA is a cell cycle-regulated kinase which ... related kinase 1, hARK1, AURKA, AIK, ARK1, AURA, BTAK, STK15, STK6, STK7, STK15, AURORA2, MGC34538. ...
Indeed, exposure of tumor cells to inhibitors of Aurora kinase (Aurk) and Polo-like kinases (Plk), key regulators of G2-M, ... Indeed, exposure of tumor cells to inhibitors of Aurora kinase (Aurk) and Polo-like kinases (Plk), key regulators of G2-M, ... Targeting sonic hedgehog-associated medulloblastoma through inhibition of Aurora and Polo-like kinases.. Targeting sonic ...
Abstract 2387: Interplay between Aurora A kinase and BRCA1 promotes genetic stability. Christine M. Marion, Vanessa Yu and ... Interplay between Aurora A kinase and BRCA1 promotes genetic stability. [abstract]. In: Proceedings of the 105th Annual Meeting ... Aurora A kinase inhibition stabilizes the metaphase checkpoint and reduces the population of proliferating polyploid/aneuploidy ... Abstract 2387: Interplay between Aurora A kinase and BRCA1 promotes genetic stability ...
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  • The recent identification of novel binding partners and key downstream effectors, together with new small-molecule inhibitors that display efficacy against tumours, heralds an upsurge of interest in these critical kinases. (nih.gov)
  • In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. (aacrjournals.org)
  • Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents. (aacrjournals.org)
  • Maleic acid is used in the synthesis of pyridoindolones as potent inhibitors of Aurora kinases. (csnpharm.com)
  • Hesperadin treatment causes defects in mitosis and cytokinesis, leading to stoppage of proliferation of HeLa cells and polyploidization, which can be specifically ascribed to the inhibition of Aurora B function during the process of chromosome attachment. (selleckchem.com)
  • Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. (aacrjournals.org)
  • The researchers noted that the role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials. (libbyshope.com)
  • The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging from the entry into mitosis, centrosome function, mitotic spindle formation, chromosome biorientation and segregation, and cytokinesis. (nih.gov)
  • The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. (aacrjournals.org)
  • Roles of Aurora kinases in mitosis and tumorigenesis[J]. Molecular Cancer Research, 2007, 5(1): 1-10. (sinobiological.com)
  • Aurora Kinase A (Aurora 2 or Serine/Threonine Protein Kinase 15 or Serine/Threonine Protein Kinase 6 or Serine/Threonine Protein Kinase Aurora A or Aurora/IPL1 Related Kinase 1 or AURKA or EC 2.7.11.1) pipeline Target constitutes close to 17 molecules. (grandresearchstore.com)
  • Aurora Kinase A (Aurora 2 or Serine/Threonine Protein Kinase 15 or Serine/Threonine Protein Kinase 6 or Serine/Threonine Protein Kinase Aurora A or Aurora/IPL1 Related Kinase 1 or AURKA or EC 2.7.11.1) - Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that contributes to the regulation of cell cycle progression. (grandresearchstore.com)
  • It also reviews key players involved in Aurora Kinase A (Aurora 2 or Serine/Threonine Protein Kinase 15 or Serine/Threonine Protein Kinase 6 or Serine/Threonine Protein Kinase Aurora A or Aurora/IPL1 Related Kinase 1 or AURKA or EC 2.7.11.1) targeted therapeutics development with respective active and dormant or discontinued projects. (grandresearchstore.com)
  • Hesperadin potently inhibits Aurora B with IC50 of 250 nM in a cell-free assay. (selleckchem.com)
  • Hesperadin inhibits the ability of immunoprecipitated Aurora B to phosphorylate histone H3 with IC50 of 250 nM and markedly reduces the activity of other kinases (AMPK, Lck, MKK1, MAPKAP-K1, CHK1, and PHK) at a concentration of 1 μM. (selleckchem.com)
  • SP-146 is a highly selective and non-ATP-competitive Aurora A/B inhibitor with IC50 values of 0.316nM 18.975 nM for Aurora A and Aurora B, respectively. (csnpharm.com)
  • This review details new developments in the field and analyses the potential of Aurora kinases as anticancer targets. (nih.gov)
  • Indeed, proteins intimately involved in the regulation of the cell cycle ( 6 ), particularly cell cycle-associated kinases ( 7 , 8 ), have been suggested as possible new anticancer targets. (aacrjournals.org)
  • Methods We used quantitative real-time reverse transcription polymerase chain reaction, immunofluorescence, immunohistochemistry, luciferase reporter, immunoblot, co-immunoprecipitation, and in vitro kinase assays to analyze AGS and MKN28 gastric cancer cells. (elsevier.com)
  • Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. (aacrjournals.org)
  • Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. (aacrjournals.org)
  • Members of the aurora kinase family regulate a range of mitotic processes. (biologists.org)
  • Overexpression of Aurora B results in multinucleation and polyploidy in human cells. (sinobiological.com)
  • However, down-regulation or overexpression of an inactive form of Aurora B yields the same polyploidization phenomenon. (sinobiological.com)
  • Overexpression of Aurora B also leads to centrosome amplification and increased ploidy, and the absence of p53 exacerbates this phenotype. (sinobiological.com)
  • It has been reported that Aurora B overexpression induces chromosomes lagging in metaphase, chromosome segregation error, and errors in cytokinesis, and thus may play a role in carcinogenesis. (sinobiological.com)
  • Depletion of Aurora B or overexpression of an inactive form in cells would also compromise the spindle checkpoint because the activity of Aurora B is required for checkpoint protein recruitment. (sinobiological.com)
  • Furthermore, Aurora B promotes inappropriate cellular mobility, which underlies invasion and metastasis of cancer cells.overexpression or nondegradation mutants could promote anchorage-independent growth in soft agar. (sinobiological.com)
  • Thus the enzyme activity, localisation and phenotype arising from our manipulations of this single fission yeast aurora kinase family member suggest that this single kinase is executing functions that are separately implemented by distinct aurora A and aurora B kinases in higher systems. (biologists.org)
  • Aurora kinases (AKs), a specific family of protein kinases , are essential for various steps in human cell division. (libbyshope.com)
  • Hesperadin and nocodazole treatment in HeLa cells abolishes kinetochore localization of BubR1 and diminishes the intensity of Bub1 at kinetochores, suggesting that Aurora B function is required for efficient kinetochore recruitment of BubR1 and Bub1, which in turn might be necessary for prolonged checkpoint signaling. (selleckchem.com)
  • Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. (aacrjournals.org)
  • Aurora 2) functions during prophase of mitosis and is required for correct function of the centrosomes (the microtubule organising centres in eukaryotic cells). (wikipedia.org)
  • The Xenopus, Drosophila, and Caenorhabditis elegans genomes, on the other hand, contain orthologues only to Aurora A and Aurora B. In all studied species, the three Aurora mitotic kinases localize to the centrosome during different phases of mitosis. (wikipedia.org)
  • Aurora A and Aurora B kinases play important roles in mitosis. (wikipedia.org)
  • Finally, Aurora A helps orchestrate an exit from mitosis by contributing to the completion of cytokinesis- the process by which the cytoplasm of the parent cell is split into two daughter cells. (wikipedia.org)
  • Though the exact mechanism by which Aurora A aids cytokinesis is unknown, it is well documented that it relocalizes to the mid-body immediately before the completion of mitosis. (wikipedia.org)
  • The Aurora kinases have been implicated in tumorigenesis and are important regulators of diverse cell cycle events, ranging from the entry into mitosis, centrosome function, mitotic spindle formation, chromosome biorientation and segregation, and cytokinesis. (nih.gov)
  • Increased Aurora A expression occurs in a variety of human cancers and induces chromosomal abnormalities during mitosis associated with tumor initiation and progression. (pnas.org)
  • Despite similarities in name and structure, Aurora A and Aurora B carry out distinct activities in mitosis. (pnas.org)
  • Aurora A is expressed early in mitosis and localizes to centrosomes and proximal mitotic spindles ( 3 ). (pnas.org)
  • Aurora B localizes to kinetochores in mitosis and to the midbody during cytokinesis ( 3 ), where it phosphorylates several proteins, including INCENP (inner centromere protein), Histone H3, and RacGAP, among others ( 4 , 14 ). (pnas.org)
  • Hesperadin treatment causes defects in mitosis and cytokinesis, leading to stoppage of proliferation of HeLa cells and polyploidization, which can be specifically ascribed to the inhibition of Aurora B function during the process of chromosome attachment. (selleckchem.com)
  • Aurora B is the catalytic component of the chromosomal passenger complex which coordinates events during segregation of the chromatids during mitosis, histone modification (epigenetic regulation) and cytokinesis. (biovision.com)
  • Additionally, we demonstrate that Aurora A kinase associates with inner centromere protein (INCENP) during mitosis and that INCENP is competent to drive accumulation of the kinase to the centromere region of mitotic chromosomes. (rupress.org)
  • These findings reveal that both Aurora A and B contribute to kinetochore-microtubule attachment dynamics, and they uncover an unexpected role for Aurora A in late mitosis. (rupress.org)
  • 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)
  • The localization of Aurora A to centrosomes and proximal microtubules is distinct from that of Aurora B and C, which bind to centromeres early in mitosis before translocating to the central spindle in anaphase and the midbody during cytokinesis. (sciencemag.org)
  • The Aurora kinases regulate key stages of mitosis including centrosome maturation, spindle assembly, chromosome segregation and cytokinesis. (aacrjournals.org)
  • Aurora B is the catalytic component of the chromosomal passenger complex (CPC), which is critical for the correct progression through and completion of mitosis. (thefreedictionary.com)
  • Aurora A kinase is activated by 2-ME in S-phase as well as during mitosis, and phosphorylates CHIP at S273. (aacrjournals.org)
  • Like for all aurora-A kinases, the Xenopus pEg2 kinase level peaks in G(2)/M and is hardly detectable in G(1) cells, suggesting that the protein is degraded upon exit from mitosis as reported for the human aurora-A kinase. (inserm.fr)
  • Therefore, there is an urgent need to research and develop new treatments and one of the recent areas of cancer research has targeted components of mitosis, mainly the mitotic kinases. (ucl.ac.uk)
  • Yeasts have a single Aurora kinase, whereas mammals have three: Aurora A, B and C. During mitosis, Aurora kinases regulate the structure and function of the cytoskeleton and chromosomes and the interactions between these two at the kinetochore. (ed.ac.uk)
  • In recent years, with the deepening of research on Aurora kinase, people have gradually recognized the important functions of Aurora kinase in cell mitosis and tumor formation. (creative-diagnostics.com)
  • In cell mitosis, Aurora kinases are involved in many events such as centrosome maturation, spindle assembly and maintenance, chromosome segregation, and cytokinesis. (creative-diagnostics.com)
  • Abnormally expressed aurora kinases tend to cause many abnormalities in the process of mitosis. (creative-diagnostics.com)
  • These three homologous aurora kinases contain a conserved C-terminal catalytic domain and an N-terminal domain of varying lengths, all of which have different localization and function during mitosis. (creative-diagnostics.com)
  • From the S phase of the cell to the end of mitosis, Aurora A is localized to the centrosome. (creative-diagnostics.com)
  • Aurora A plays an important role in mitosis. (creative-diagnostics.com)
  • Inhibition of Aurora A activity by RNAi delays cell entry into the mitosis phase, whereas overexpression can impair spindle checkpoint function and inhibit cytokinesis. (creative-diagnostics.com)
  • In the early stage of mitosis, Aurora B is distributed along the chromosome arm and then aggregates on the centromere of the chromosome and remains until the middle of the division. (creative-diagnostics.com)
  • Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors. (escholarship.org)
  • The Aurora A kinase is associated with centrosome maturation and separation and thereby regulates spindle assembly and stability. (wikipedia.org)
  • The Aurora B kinase is a chromosome passenger protein and regulates chromosome segregation and cytokinesis. (wikipedia.org)
  • The present review focuses on how Aurora B regulates attachments in response to centromere tension. (biochemsoctrans.org)
  • Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. (sciencemag.org)
  • Metazoans appear to contain three distinct aurora-related kinases, each one of which regulates a different set of mitotic events. (biologists.org)
  • In each system, aurora A kinase controls spindle formation while aurora B kinase regulates chromosome disjunction and cytokinesis. (biologists.org)
  • Very recent studies have revealed that Aurora A acts as a positive regulator of the Yes-associated protein (YAP), a downstream effector in the Hippo pathway, which regulates tissue homeostasis and organ size during development. (bellbrooklabs.com)
  • We show that the aurora-B kinase AIR-2 regulates the selective release of chromosome cohesion during Caenorhabditis elegans meiosis. (rupress.org)
  • Aurora A regulates centrosome function during M phase and is required for initial activation of CDK1 at centrosomes and phosphorylates numerous target proteins. (roche.com)
  • Aurora B is also one of the essential kinases for normal cytokinesis, which regulates various stages of cytokinesis through different substrate molecules. (creative-diagnostics.com)
  • Aurora-C interactions with members of the Chromosome Passenger Complex ( CPC ), Survivin (zeige BIRC5 Antikörper ) and Inner Centromere Protein (INCENP (zeige INCENP Antikörper )) in reference to known Aurora-B (zeige AURKB Antikörper ) interactions to understand the functional significance of Aurora-C overexpression in human cancer cells, is reported. (antikoerper-online.de)
  • 279 Aurora Kinase B (AURKB) Antibodies from 32 manufacturers are available on www.antibodies-online.com. (antibodies-online.com)
  • Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). (gla.ac.uk)
  • SNS-314, a novel aminothiazole-derived urea, is a selective inhibitor of Aurora kinases A, B, and C with IC 50 values in the low nanomolar range. (aacrjournals.org)
  • Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. (nih.gov)
  • The phylogenetic analysis of available Aurora sequences from different eukaryotic origins suggests that, although a plant Aurora gene has been duplicated early in the evolution of plants, the paralogs nevertheless maintained a role in cell cycle-related signal transduction pathways. (uniprot.org)
  • The major signaling pathways activated by EGFR are the RAS-RAF-MAP kinase pathway, which is mainly involved in proliferation, and the PI3K-PTEN-AKT pathway, which is mainly involved in survival [ 16 ]. (oncotarget.com)
  • Recent findings on the interactions of Aurora kinases with tumor suppressor gene and oncogene-regulated networks as well as involvement in other nonmitotic processes such as ciliary disassembly affecting important signaling pathways and developmental disorders termed ciliopathies, have led to a greater recognition of the functional significance of these kinases in development and disease. (elsevier.com)
  • Among the three members of the kinase family, Aurora- A, -B, and -C identified in humans, Aurora-A and -B have been reported to express at detectable levels in most proliferating somatic cells and characterized in detail for their involvement in cellular pathways relevant to cell proliferation and development of cancer-associated phenotypes. (elsevier.com)
  • Millennium, a unit of Takeda Pharmaceutical Co. Ltd., may soon be able to add peripheral T-cell lymphoma (PTCL) to its list of cancers that can be treated with its investigational Aurora A kinase inhibitor, MLN8237 (alisertib). (bioworld.com)
  • In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. (eurekaselect.com)
  • What have these studies taught us about the therapeutic potential of inhibiting this family of kinases? (nih.gov)
  • Aurora kinases: shining lights on the therapeutic horizon? (nih.gov)
  • Using gene expression profiling, aurora kinase inhibitors as a promising therapeutic option in myeloma can be tailoredly given to patients expressing aurora-A, who in turn have an adverse prognosis. (nih.gov)
  • In human tumor xenografts, MLN8054 induced mitotic accumulation and apoptosis, phenotypes consistent with inhibition of Aurora A. MLN8054 is a selective inhibitor of Aurora A kinase that robustly inhibits growth of human tumor xenografts and represents an attractive modality for therapeutic intervention of human cancers. (pnas.org)
  • Aurora-A conditional mutant mice provide a valuable system for further defining Aurora-A functions and for predicting effects of Aurora-A therapeutic intervention. (asm.org)
  • These results reveal a novel 2-ME→Aurora A→CHIP→AR pathway which promotes AR degradation via the proteasome, that may offer novel therapeutic opportunities for prostate cancer. (aacrjournals.org)
  • An intensive research effort over the past decade has led to the discovery of chemically distinct families of small molecule Aurora kinase inhibitors, many of which have demonstrated therapeutic potential in model systems. (semanticscholar.org)
  • Aurora-A Kinase as a Promising Therapeutic Target in Cancer. (bellbrooklabs.com)
  • Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)
  • Aurora Kinase B - Pipeline Review, H2 2018 - ResearchAndM. (pharmiweb.com)
  • The "Aurora Kinase B - Pipeline Review, H2 2018" drug pipelines has been added to ResearchAndMarkets.com's offering. (pharmiweb.com)
  • In 2017, the global Aurora Kinase C market size was xx million US$ and it is expected to reach xx million US$ by the end of 2025, with a CAGR of xx.x % between 2018 and 2025. (rnrmarketresearch.com)
  • To analyze and study the global Aurora Kinase C sales, value, status (2013-2017) and forecast (2018-2025). (rnrmarketresearch.com)
  • Besides being implicated as mitotic regulators, these three kinases have generated significant interest in the cancer research field due to their elevated expression profiles in many human cancers. (wikipedia.org)
  • Indeed, exposure of tumor cells to inhibitors of Aurora kinase (Aurk) and Polo-like kinases (Plk), key regulators of G2-M, induces cell-cycle arrest, apoptosis, and enhanced sensitivity to conventional chemotherapy. (ca.gov)
  • The families of cyclin-dependent (Cdk), Aurora, and Polo-like (Plk) kinases have emerged as the primary regulators of cell division. (sciencemag.org)
  • Multiple regulators, many of which are kinases, are required to ensure that each event is completed in a timely fashion and in the proper order (reviewed in reference 46 ). (asm.org)
  • The Aurora kinases are key mitotic regulators in eukaryotes (reviewed in reference 45 ). (asm.org)
  • 1] Mitotic kinases as regulators of cell division and its checkpoints. (axonmedchem.com)
  • Especially protein kinases are important regulators of virus-host interaction indicated by remarkable kinome alterations induced upon HCMV infection. (ovid.com)
  • This suggests that Aurora Kinase 2 can behave as a dominant negative mutant and inhibit other aurora kinases. (leicabiosystems.com)
  • and 3) agents that inhibit Aurora activity would be expected to increase AR levels and signaling, thereby promoting prostate cancer growth. (aacrjournals.org)
  • The recent identification of novel binding partners and key downstream effectors, together with new small-molecule inhibitors that display efficacy against tumours, heralds an upsurge of interest in these critical kinases. (nih.gov)
  • Small-molecule inhibitors of human Aurora kinases have been identified by several groups. (pnas.org)
  • The involvement of these kinases in cell division and deregulated expression of aurora A and B in tumor cells (often resulting in genetic aberrations and thus leading to malignancy) together provided the incentive to identify and test small-molecule inhibitors of these kinases. (biovision.com)
  • Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237. (semanticscholar.org)
  • The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. (springer.com)
  • Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin. (biomedcentral.com)
  • In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. (plos.org)
  • The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. (plos.org)
  • To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. (jcancer.org)
  • On the basis of these results, several confirmatory single-agent and combination studies have been initiated using alisertib and other inhibitors of aurora kinases in lymphoma. (ascopost.com)
  • Maleic acid is used in the synthesis of pyridoindolones as potent inhibitors of Aurora kinases. (csnpharm.com)
  • Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. (plos.org)
  • However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients. (plos.org)
  • Considering that Aurora kinase inhibitors are currently under clinical investigation in hematologic cancers, the identification of molecular events that limit the response to such agents is essential for enhancing clinical outcomes. (haematologica.org)
  • The functional relevance of this newly discovered regulatory axis is found to be highly correlated with triple-negative breast cancer, suggesting that an inhibitor for Aurora A will be valuable in similar cancers. (bellbrooklabs.com)
  • Additionally, Aurora A kinase plays an unexpected role in systematic tumor recurrences of glioblastoma, which opens new possibilities for selective inhibitors in treating one of the deadliest cancers. (bellbrooklabs.com)
  • Over-expression of Aurora-A or -B protein can lead to aneuploid cells and is frequently observed in various human cancers such as prostate, breast, and esophageal cancers. (roche.com)
  • The effect of the clinical Aurora-kinase inhibitor VX680 on proliferation of 20 human-myeloma-cell-lines and survival of 5 primary myeloma-cell-samples was tested. (archives-ouvertes.fr)
  • We identified for the first time a sequence RxxL in the C-terminal end of the kinase catalytic domain. (inserm.fr)
  • Three aurora kinases have been identified in humans and designated as Aurora-A, -B, and -C. They mostly consist of two domains: a regulatory domain in the NH2 terminus and a catalytic domain in the COOH terminus. (roche.com)
  • We therefore hypothesize that forced alterations in Aurora A expression may influence this process by acting, directly or indirectly, as an upstream regulator of BRCA1 expression, thereby preventing polyploidy and stabilizing the genome. (aacrjournals.org)
  • The reduced activity of Aurora B kinase resulted in polyploidy and suppression of cancer cell viability. (oup.com)
  • More specifically, Aurora kinases play a crucial role in cellular division by controlling chromatid segregation. (wikipedia.org)
  • Although there is evidence to suggest that Aurora C might be a chromosomal passenger protein, the cellular function of it is less clear. (wikipedia.org)
  • Genetic instability and cellular proliferation have been associated with aurora kinase expression in several cancer entities, including multiple myeloma. (nih.gov)
  • Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 was demonstrated in enzymatic and cellular assays. (aacrjournals.org)
  • In addition to predicting previously unknown functions, this work establishes additional substrate-recognition motifs for these kinases and provides an analytical template for further use in dissecting kinase signaling events in other areas of cellular signaling and systems biology. (sciencemag.org)
  • Here we report a novel approach of kinome profiling with an outcome that suggests an important role of specific cellular protein kinases, such as AMPK, ABL2 and Aurora A. Inhibition of AMPK and ABL kinases showed a significant reduction, whereas inhibition of Aurora A kinase led to a slight activation of HCMV replication, as measured in a GFP reporter-based replication assay. (ovid.com)
  • The cellular geography of aurora kinases. (bellbrooklabs.com)
  • Aurora kinases are strongly expressed in a broad range of cancer types. (aacrjournals.org)
  • The expression of aurora C in cancer is less well studied. (aacrjournals.org)
  • MLN8054 was the first orally administered Aurora A–selective inhibitor to be tested in human clinical trials for the treatment of colorectal cancer. (biovision.com)
  • [1] A recent study shows that MLN8054 sensitizes androgen-resistant prostate cancer to radiation by inhibiting Aurora A kinase, which is associated with sustained DNA double-strand breaks. (selleckchem.com)
  • The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. (plos.org)
  • Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. (eurekaselect.com)
  • Moreover, aberrant expression of YAP and Aurora A signaling is highly correlated with triple-negative breast cancer (TNBC). (ovid.com)
  • Perturbation of Aurora kinase expression or function might lead to cancer. (ed.ac.uk)
  • Among the down-regulated genes revealed by cDNA microarray analyses, we identified Aurora-A, a centrosome kinase that plays a critical role in regulating M phase events and is frequently amplified in several types of cancer. (uniprot.org)
  • In addition, Aurora kinase is involved in the process of tumor formation, and it has been found that some small molecules that target the aurora kinases have significant anti-cancer effects. (creative-diagnostics.com)
  • This suspected oncogenic role of Aurora A, in addition to its essential role in mitotic progression, make it an attractive target for anticancer therapy. (pnas.org)
  • In addition, disruption of Aurora A protein in tumor cells delays mitotic entry and progression, resulting in the accumulation of cells in the G 2 /M cell cycle phase ( 9 - 13 ). (pnas.org)
  • Increased Aurora A expression may lead to increased kinase activity, which is thought to contribute to tumor initiation and progression ( 20 ). (pnas.org)
  • This paper reviews studies on Aurora kinases from recent years, including studies of their biological function, their relationship with tumor progression, and their inhibitors. (eurekaselect.com)
  • We have identified the microtubule-bundling protein MAP65-1 as a substrate for alpha Aurora kinases (Boruc et al. (ugent.be)
  • It has recently been demonstrated that Coenzyme A (CoA) is a highly selective ATP-competitive inhibitor of Aurora A kinase. (ucl.ac.uk)
  • SP-146 is a highly selective and non-ATP-competitive Aurora A/B inhibitor with IC50 values of 0.316nM 18.975 nM for Aurora A and Aurora B, respectively. (csnpharm.com)
  • Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Aurora inhibitors. (rcsb.org)
  • Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. (asm.org)