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.
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
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
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
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.

Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. (1/287)

BACKGROUND: In animal cells, cytokinesis begins shortly after the sister chromatids move to the spindle poles. The inner centromere protein (Incenp)has been implicated in both chromosome segregation and cytokinesis, but it is not known exactly how it mediates these two distinct processes. RESULTS: We identified two Caenorhabditis elegans proteins, ICP-1 and ICP-2, with significant homology in their carboxyl termini to the corresponding region of vertebrate Incenp. Embryos depleted of ICP-1 by RNA-mediated interference had defects in both chromosome segregation and cytokinesis. Depletion of the Aurora-like kinase AIR-2 resulted in a similar phenotype. The carboxy-terminal region of Incenp is also homologous to that in Sli15p, a budding yeast protein that functions with the yeast Aurora kinase Ipl1p. ICP-1 bound C. elegans AIR-2 in vitro, and the corresponding mammalian orthologs Incenp and AIRK2 could be co-immunoprecipitated from cell extracts. A significant fraction of embryos depleted of ICP-1 and AIR-2 completed one cell division over the course of several cell cycles. ICP-1 promoted the stable localization of ZEN-4 (also known as CeMKLP1), a kinesin-like protein required for central spindle assembly. CONCLUSIONS: ICP-1 and AIR-2 are part of a complex that is essential for chromosome segregation and for efficient completion of cytokinesis. We propose that this complex acts by promoting dissolution of sister chromatid cohesion and the assembly of the central spindle.  (+info)

Alternative splicing in 5'-untranslational region of STK-15 gene, encoding centrosome associated kinase, in breast cancer cell lines. (2/287)

Centrosomes maintain genomic stability by establishing the bipolar spindles during cell division and, execute accurate segregation of chromosomes during mitosis. In this study, we have demonstrated that there are three forms of STK-15 gene in breast cancer cell lines. Alternative splice positions are located in 5'-untranslated region of STK15 gene. The results of in vitro translation experiments revealed that the alternative splicing in the 5'-untranslated region of STK15 had no effect on protein translation. The differential expression patterns of these alternatively spliced STK15 in breast cell lines and primary tumors therefore suggest that STK15 gene transcription may be differentially regulated or stabilized in these cells.  (+info)

Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. (3/287)

Our recent analysis of gastric cancers using comparative genomic hybridization (CGH) revealed a novel high frequent copy number increase in the long arm of chromosome 20. Tumour-amplified kinase BTAK was recently cloned from breast cancers and mapped on 20q13 as a target gene for this amplification in human breast cancers. In the study presented here, we analysed BTAK copy-number and expression, and their relation to the ploidy pattern in 72 primary gastric cancers. Furthermore, wild-type BTAK and its deletion mutants were transfected to gastric cancers to examine changes in cell proliferation and DNA ploidy pattern. Evaluation of 72 unselected primary gastric cancers found BTAK amplification in 5% and overexpression in more than 50%. All four clinical samples with BTAK amplification showed aneuploidy and poor prognosis. Transfection of BTAK in near-diploid gastric cancers induced another aneuploid cell population. In contrast, the c-terminal-deleted mutant of BTAK induced no effect in DNA ploidy pattern and inhibited gastric cancer cell proliferation. These results suggest that BTAK may be involved in gastric cancer cell aneuploid formation, and is a candidate gene for the increase in the number of copies of the 20q, and thus may contribute to an increase in the malignant phenotype of gastric cancer.  (+info)

Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells. (4/287)

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.  (+info)

Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. (5/287)

STK15 is an Aurora/Ipl-1 related serine/threonine kinase that is associated with centrosomes and induces aneuploidy when overexpressed in mammalian cells. It is well known that phosphorylation and dephosphorylation of kinases are important for regulation of their activity. But mechanisms by which STK15 activity is regulated have not been elucidated. We report that STK15 contains two functional binding sites for protein phosphatase type 1 (PP1), and the binding of these proteins is cell cycle-regulated peaking at mitosis. Activated STK15 at mitosis phosphorylates PP1 and inhibits PP1 activity in vitro. In vivo, PP1 activity co-immunoprecipitated with STK15 is also reduced. These data indicate that STK15 inhibits PP1 activity during mitosis. Also, PP1 is shown to dephosphorylate active STK15 and abolish its activity in vitro. Furthermore, we show that non-binding mutants of STK15 for PP1 are superphosphorylated, but their kinase activities are markedly reduced. Cells transfected with these non-binding mutants manifest aberrant chromosome alignment during mitosis. Our results suggest that a feedback regulation through phosphorylation/dephosphorylation events between STK15 kinase and PP1 phosphatase operates through the cell cycle. Deregulation of this balance may contribute to anomalous segregation of chromosomes during mitotic progression of cancer cells.  (+info)

Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. (6/287)

Centrosomes mature as cells enter mitosis, accumulating gamma-tubulin and other pericentriolar material (PCM) components. This occurs concomitant with an increase in the number of centrosomally organized microtubules (MTs). Here, we use RNA-mediated interference (RNAi) to examine the role of the aurora-A kinase, AIR-1, during centrosome maturation in Caenorhabditis elegans. In air-1(RNAi) embryos, centrosomes separate normally, an event that occurs before maturation in C. elegans. After nuclear envelope breakdown, the separated centrosomes collapse together, and spindle assembly fails. In mitotic air-1(RNAi) embryos, centrosomal alpha-tubulin fluorescence intensity accumulates to only 40% of wild-type levels, suggesting a defect in the maturation process. Consistent with this hypothesis, we find that AIR-1 is required for the increase in centrosomal gamma-tubulin and two other PCM components, ZYG-9 and CeGrip, as embryos enter mitosis. Furthermore, the AIR-1-dependent increase in centrosomal gamma-tubulin does not require MTs. These results suggest that aurora-A kinases are required to execute a MT-independent pathway for the recruitment of PCM during centrosome maturation.  (+info)

Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. (7/287)

Phosphorylation at a highly conserved serine residue (Ser-10) in the histone H3 tail is considered to be a crucial event for the onset of mitosis. This modification appears early in the G(2) phase within pericentromeric heterochromatin and spreads in an ordered fashion coincident with mitotic chromosome condensation. Mutation of Ser-10 is essential in Tetrahymena, since it results in abnormal chromosome segregation and extensive chromosome loss during mitosis and meiosis, establishing a strong link between signaling and chromosome dynamics. Although mitotic H3 phosphorylation has been long recognized, the transduction routes and the identity of the protein kinases involved have been elusive. Here we show that the expression of Aurora-A and Aurora-B, two kinases of the Aurora/AIK family, is tightly coordinated with H3 phosphorylation during the G(2)/M transition. During the G(2) phase, the Aurora-A kinase is coexpressed while the Aurora-B kinase colocalizes with phosphorylated histone H3. At prophase and metaphase, Aurora-A is highly localized in the centrosomic region and in the spindle poles while Aurora-B is present in the centromeric region concurrent with H3 phosphorylation, to then translocate by cytokinesis to the midbody region. Both Aurora-A and Aurora-B proteins physically interact with the H3 tail and efficiently phosphorylate Ser10 both in vitro and in vivo, even if Aurora-A appears to be a better H3 kinase than Aurora-B. Since Aurora-A and Aurora-B are known to be overexpressed in a variety of human cancers, our findings provide an attractive link between cell transformation, chromatin modifications and a specific kinase system.  (+info)

Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1. (8/287)

Human aurora A is a serine-threonine kinase that controls various mitotic events. The transcription of aurora A mRNA varies throughout the cell cycle and peaks during G(2)/M. To clarify the transcriptional mechanism, we first cloned the 1.8-kb 5'-flanking region of aurora A including the first exon. Transient expression of aurora A promoter-luciferase constructs containing a series of 5'-truncated sequences or site-directed mutations identified a 7-bp sequence (CTTCCGG) from -85 to -79 as a positive regulatory element. Electromobility shift assays identified the binding of positive regulatory proteins to the CTTCCGG element. Anti-E4TF1-60 antibody generated a supershifted complex. Furthermore, coexpression of E4TF1-60 and E4TF1-53 markedly increased aurora A promoter activity. Synchronized cells transfected with the aurora A promoter-luciferase constructs revealed that the promoter activity of aurora A increased in the S phase and peaked at G(2)/M. In addition, we identified a tandem repressor element, CDE/CHR, just downstream of the CTTCCGG element, and mutation within this element led to a loss of cell cycle regulation. We conclude that the transcription of aurora A is positively regulated by E4TF1, a ubiquitously expressed ETS family protein, and that the CDE/CHR element was essential for the G(2)/M-specific transcription of aurora A.  (+info)

In this report, we have shown that Aurora-A, a centrosome-associated oncogenic protein, is overexpressed in human ESCC. Using an immunochemical staining approach, we found about 69% (45 of 64 samples) of ESCC tumor tissues to strongly overexpress Aurora-A protein. In contrast, ,2% (1 of 61 samples) of normal adjacent tissues displayed high expression of Aurora-A (Fig. 1⇓ ; Table 1⇓ ). These findings were further confirmed by Western blot analysis (Fig. 2)⇓ . Interestingly, overexpression of Aurora-A was shown to associate with the grades of tumor differentiation and invasive capability. Additionally, we have also examined Aurora-A expression and cell migration in 12 human ESCC lines and found that levels of Aurora-A protein were correlated to the migrating potentials of tumor cells. Moreover, disruption of endogenous Aurora-A protein through siRNA knockdown technique was shown to substantially suppress cell migration (Fig. 4)⇓ , suggesting an association of Aurora-A with tumor cell ...
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 ...
Aurora kinase A inhibition with alisertib monotherapy may benefit a subset of patients with neuroendocrine prostate cancer (NEPC).
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: 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 ...
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 ...
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 ...
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 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 ...
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.
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 …
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. ...
Multiple proof-of-principle experiments suggest that targeting members of the Myc family of oncoproteins will have significant therapeutic benefit in human tumors. Deregulated expression of MYCN, one of the three family members implicated in human tumors, is prevalent in both pediatric and adult neuroendocrine tumors. We have shown previously that MYCN-amplified neuroblastoma cells depend on high levels of Aurora-A expression for maintaining N-Myc function. Similarly, Aurora-A and N-Myc bind each other and together drive an oncogenic gene expression program in neuroendocrine prostate tumors. Although stabilization of N-Myc does not require the catalytic activity of Aurora-A, we found that two inhibitors of Aurora-A disrupt the Aurora-A/N-Myc complex and promote degradation of N-Myc via the Fbxw7 ubiquitin ligase. Disruption of the Aurora-A/N-Myc complex inhibits N-Myc-dependent transcription, correlating with tumor regression and prolonged survival in a mouse model of MYCN-driven neuroblastoma, ...
Inhibitors,Activator,Agonist,antagonist,API,Aurora,Metabolic Disease,VEGFR-PDGFR,Other Intermediate,Others,MOF Chemicals,,Active Biopharma Corp
Although the MAPK pathway is frequently deregulated in cancer, inhibitors targeting RAF or MEK have so far shown clinical activity only in BRAF- and NRAS-mutant melanoma. Improvements in efficacy may be possible by combining inhibition of mitogenic signal transduction with inhibition of cell-cycle progression. We have studied the preclinical pharmacology of BI 847325, an ATP-competitive dual inhibitor of MEK and Aurora kinases. Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 was demonstrated in enzymatic and cellular assays. Equipotent effects were observed in BRAF-mutant cells, whereas in KRAS-mutant cells, MEK inhibition required higher concentrations than Aurora kinase inhibition. Daily oral administration of BI 847325 at 10 mg/kg showed efficacy in both BRAF- and KRAS-mutant xenograft models. Biomarker analysis suggested that this effect was primarily due to inhibition of MEK in BRAF-mutant models but of Aurora kinase in KRAS-mutant models. Inhibition of both MEK and Aurora ...
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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.
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 ...
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 ...
Senescence-inducing therapies can block proliferation of malignant cells and promote anti-tumor immune activity. However, the risk of tumor relapse remains high due to the long lifespan of senescence cells with potential to escape senescence. Here our preclinical studies demonstrate that combining a senescent-inducing aurora kinase A (AURKA) inhibitor alisertib (MLN8237) with an MDM2 antagonist [(-)-nutlin 3a] effectively induces robust p53 activation in senescent Tp53WT tumors accompanied by: 1) tumor cell proliferation arrest; 2) mitochondrial depolarization and tumor cell apoptosis; and 3) tumor cell clearance via CCL5-, CCL1- and CCL9-mediated recruitment of anti-tumor leukocytes. This combined therapy shows adequate bioavailability and low toxicity to the host in the mouse model. Moreover, the prominent preclinical response of patient-derived melanoma tumors to the co-targeting of MDM2 and AURKA provides rationale for further investigation of alisertib and MDM2 inhibitors.. Citation Format: ...
Integration of metabolic and immune system responses during pet advancement guarantees energy stability permitting both protection and development. energy death and imbalance. Hyperactive proinflammatory and tension signaling through NF-κB/Relish Jun N-terminal kinase and FOXO in mutants deregulates genes very important to immune defense digestive function and lipid fat burning capacity. Reducing the dose of either FOXO or Relish normalizes both lipid gene and metabolism expression in mutants. The function of Atf3 is normally conserved as individual ATF3 averts a number of the mutant phenotypes enhancing their survival. The single Atf3 might incorporate the varied roles of two related mammalian proteins. INTRODUCTION Animal development and development depend on coordinated features of body organs to stability energy intake and storage space under optimum or challenging circumstances such as meals scarcity or pathogen strike. When unfortunate circumstances are temporary pets survive by ...
virulence, which reflects the events occurring in the murine illness model, renal M-1 cortical collecting duct epithelial cells were evaluated while the early suppliers of cytokines in response to cells capable of forming hyphae, producing chemokines KC and MIP-2, with levels correlating with epithelial cell damage. most important nosocomial infections in Europe and the US and is definitely connected with high mortality (40%) rates among hospitalized individuals, particularly those in extensive care models (ICU), people undergoing major surgery treatment and in immunocompromised individuals.2-6 Mucosal and systemic candidiasis is mainly studied in animal models.7-10 However, there are limitations to these choices; is definitely not a organic colonizer of small mammals10 and there are honest and cost ramifications.11,12 These disadvantages, as well as Societys want to reduce the figures of animals used in study, possess urged scientists to explore in vitro models to refine, reduce, or replace ...
Mouse monoclonal antibody raised against partial recombinant human AURKA. Recombinant protein corresponding to amino acids 1-157 of human AURKA. (MAB17869) - Products - Abnova
Xenografts were removed, minced into 1 mm pieces, and dissociated, 0. 8 unitsml Dispase, and 100 unitsml penicillin JNJ-7706621 Aurora Kinase inhibitor strepto
Javier Pinilla-Ibarz, MD, PhD, and Naval Daver, MD, describe some of the emerging therapies for chronic myeloid leukemia, such as aurora kinase inhibitors, and how treatment discontinuation is becoming a reality.
Expression of AURKA (AIK, ARK1, AurA, BTAK, PPP1R47, STK15, STK6, STK7) in lung tissue. Antibody staining with HPA002636 and CAB001454 in immunohistochemistry.
This is an open-label, multicenter, phase 1 study of alisertib in East Asian patients (eg, patients from countries including but not limited to Singapor
Aurora A antibody [1F8] (aurora kinase A) for ELISA, FACS, ICC/IF, WB. Anti-Aurora A mAb (GTX60391) is tested in Human, Monkey, Rat samples. 100% Ab-Assurance.
Aurora A (phospho Thr288) antibody (aurora kinase A) for ICC/IF, IHC-P, WB. Anti-Aurora A (phospho Thr288) pAb (GTX85609) is tested in Human samples. 100% Ab-Assurance.
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3GZN: Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.
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 ...
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
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 ...
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 ...
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 ...
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: 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 ...
Udayakumar T.S., Belakavadi M., Choi K.-H., Pandey P.K., Fondell J.D.. The TRAP/Mediator coactivator complex serves as a functional interface between DNA-bound transactivators and the RNA polymerase II-associated basal transcription apparatus. TRAP220/MED1 is a variably associated subunit of the complex that plays a specialized role in selectively targeting TRAP/Mediator to specific genes. Ablation of the Trap220/Med1 gene in mice impairs embryonic cell growth, yet the underlying mechanism is unknown. In this report, we identified distinct cell growth regulatory genes whose expression is affected by the loss of TRAP220/MED1 by RNA interference. 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. In general, we found that TRAP220/MED1 expression is required for high basal levels of Aurora-A gene expression and that ectopic ...
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.
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 ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
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 ...
Weve provided evidence which the stimulatory ramifications of (?)-epicatechin ((?)-EPI) in endothelial cell nitric oxide (Zero) production might involve the involvement of the cell-surface receptor. usage of siRNA the function that GPER is wearing mediating ERK1/2 activation by (?)-EPI. GPER is apparently combined to a non Gi/o or Gs, proteins subtype. To extrapolate our results for an model, we utilized phenylephrine pre-contracted aortic bands evidencing that (?)-EPI may mediate vasodilation through GPER activation. To conclude, we provide proof that suggests the GPER being a potential mediator of (?)-EPI effects and highlights the key role that GPER may possess in heart protection. research. As previously reported by us, weve mixed MD simulations and docking research to explore the ligand binding sites of GPER (21). Weve centered on 14 and 70 ns conformers retrieved from MD simulations for the next docking evaluation as these conformers had been capable to acknowledge G1 and G15 in the ...
AURKA (Aurora A) is a serinethreonine kinase that regulates mitosis by association in vivo with centrosomes. Overexpression of AURKA is observed in many types of cancer.
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 ...
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.. ...
Monoklonale und polyklonale Aurora Kinase C Antikörper für viele Methoden. Ausgesuchte Qualitäts-Hersteller für Aurora Kinase C Antikörper. Hier bestellen.
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system. This system configures binary tools and library paths for you in a very flexible way. Read more about it in Lunarc documentation here: http://lunarc-documentation.readthedocs.io/en/latest/aurora_modules/ If you are in need of a module that is not installed, please check this list: https://github.com/hpcugent/easybuild-easyconfigs/tree/master/easybuild/easyconfigs If the software you need is in the list but NOT in Aurora, report to Florido, and he will coordinate with Lunarc to provide such software. If that module does not exist in the system nor in the above list, you will have to build it and configure yourself. Read more about it in the Custom software paragraph. ...
... encoding Aurora-A kinase) to regulate cell cycle[31] and ciliary resorption;[32] it is possible that CASS4 may similarly ... "The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome". Nature ... protein tyrosine kinase binding. Cellular component. • cytoplasm. • cell junction. • cytoskeleton. • focal adhesion. • cell ... interact with aurora-A kinase. Thrombosis[edit]. CASS4 signaling may contribute to platelet activation and aggregation. A PKA/ ...
This process is associated with Aurora B Protein Kinase. When Aurora B's function is disrupted, MCAK ability to locate ... Andrews PD, Ovechkina Y, Morrice N, Wagenbach M, Duncan K, Wordeman L, Swedlow JR (February 2004). "Aurora B regulates MCAK at ... There are other environments in which MCAK's function is impaired, absent impact on its associated kinase. For example, alpha- ...
"Cyclin Dependent Kinase (CDK) and Aurora Kinase (AK) inhibitors , Cyclacel R&D for anticancer drugs acting on cell cycle". www. ...
... 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 ...
Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP ... and aurora-B kinase during male mouse meiosis". J. Cell Sci. 116 (Pt 6): 961-74. doi:10.1242/jcs.00330. PMID 12584241.. ... "Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells". Chromosoma. 110 ( ... The ARK binding region has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has ...
"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. The current scientific understanding of primary cilia views ... Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (June 2007). "HEF1-dependent Aurora A activation induces ...
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 ...
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- ...
"Drugging MYCN through an Allosteric Transition in Aurora Kinase A." Cancer Cell. 26 (3): 414-27. doi:10.1016/j.ccr.2014.07.015 ... 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. ...
Aurora B is a kinase active in late metaphase, and has been shown to function as a checkpoint for the proper attachments of ... Cimini, Daniela; Wan, Xiaohu; Hirel, Christophe B.; Salmon, E.D. (2006-09-05). "Aurora Kinase Promotes Turnover of Kinetochore ... When Aurora B was partially inhibited by a small molecule drug, Cimini et al. observed lagging chromatids at increasing ... "The Ska complex promotes Aurora B activity to ensure chromosome biorientation". The Journal of Cell Biology. 215 (1): 77-93. ...
"Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research. 26 (5A): 3585-93 ...
... is also important in activating and recruiting Aurora A kinase, a kinase responsible for phosphorylating TPX2 and ... In the presence of nuclear import factor importin α, TPX2 is bound and prevented from binding Aurora A kinase, though it is ... TPX2 recruits and activates Aurora A kinase by utilizing its short 43 amino acid long amino-terminal sequence to bind the ... Notably, this recognition between TPX2 and Aurora A is analogous to that between the cAMP-dependent protein kinase (cAPK) ...
"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: ...
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- ...
2005). "The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase". Genes Cells. 9 (5): 383-97. doi:10.1111/ ... 2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076-86. doi: ... Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the LATS2 gene. This gene encodes a serine/ ... It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle ...
... 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 ...
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 ...
Aurora B kinase is produced in all dividing cells in normal tissue however; the levels of Aurora B kinase are abnormally raised ... The Aurora B kinase protein (also known as STK12) is one of a family of proteins that plays an essential role in the alignment ... Inhibition of Aurora B kinase by BI 811283 in cancer cells leads to the formation of cells with severely abnormal numbers of ... BI 811283 may be active in a range of malignancies that are known to have raised levels of Aurora B kinase including; non-small ...
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 ...
"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) ...
He S, Yang S, Deng G, Liu M, Zhu H, Zhang W, Yan S, Quan L, Bai J, Xu N (2010). "Aurora kinase A induces miR-17-92 cluster ... "miR-17-5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat ...
... (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 ...
"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 ... Oh, Sung Aeong; Bourdon, Valérie; Dickinson, Hugh G.; Twell, David; Park, Soon Ki (2014-03-01). "Arabidopsis Fused kinase TWO- ... The essential mechanism of MAPK cascade for phragmoplast expansion is suppressed by cyclin dependent kinase (CDK) activity ...
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/ ...
"Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry". Science. 320 (5883): 1655-1658 ... This loop is further amplified indirectly through the coordinated interaction of the Aurora A kinase and the Bora cofactor. ... pathways which activate the Chk2 and Chk1 kinases, respectively. These kinases act upstream of Cdc25 and Wee1, the direct ... The main rad3 effector is the kinase Chk1, which is required for the G2-M arrest in response to DNA-damaging agents. Chk1 is an ...
Seki A, Coppinger JA, Jang CY, Yates JR, Fang G (June 2008). "Bora and the kinase Aurora a cooperatively activate the kinase ... These kinases phosphorylate and activate the effector kinases Chk2 and Chk1, respectively, which in turn phosphorylate the ... The G1 phase cyclin-dependent kinase works together with S phase cyclin-dependent kinase targeting p27 for degradation. In turn ... The cell is once more examined for sites of DNA damage or incomplete replication, and the kinases ATR and ATM are recruited to ...
2006). "The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A". Mol. Cell. 20 (2): 237-49. doi:10.1016 ...
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 ...
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 ...
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, ...
... there are three classes of aurora kinases in multicellular organisms, including humans: Aurora A (a.k.a. Aurora 2) functions ... Aurora kinases are serine/threonine kinases that are essential for cell proliferation. They are phosphotransferase enzymes that ... 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 ...
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 ...
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. ...
... Biochem Soc Trans. 2009 Oct;37(Pt 5):976-80. doi: 10.1042/ ... Destabilization of incorrect attachments requires the Ipl1/Aurora B kinase, which phosphorylates kinetochore substrates that ... The present review focuses on how Aurora B regulates attachments in response to centromere tension. ...
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) ...
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 ...
VX-680 inhibits Aurora A and Aurora B kinase activity in human cells.. Tyler RK1, Shpiro N, Marquez R, Eyers PA. ... VX-680, also known as MK-0457, is a member of a diverse group of small molecules that inhibit the Aurora kinases, and has shown ... Taken together, these data identify Aurora A and Aurora B as dual intracellular targets of VX-680. ... consistent with inhibition of the mitotic protein kinase Aurora B. In this study, we have investigated the effects of VX-680 in ...
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 ...
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, ...
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 pipeline Target ...
Aurora kinase A AURKA role in cancer, overall survival in patients with bladder cancer, sequential gene expression profiling, ... The Role of Aurora Kinase A in Bladder Cancer - Expert Commentary May 15, 2019 Aurora kinase A (AURKA) plays a vital role in ...
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 Kinases as Druggable Targets in Cancer Therapy » Blog Archives Menu Not Found. Skip to content *Home ...
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, ...
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 ...
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 ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
... 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 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. ...
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 ...
Weitere Produktkategorien zu Aurora Kinase A and Ninein Interacting Protein Antikörper * 24 anti-Aurora Kinase A and Ninein ... Weitere Antikörper gegen Aurora Kinase A and Ninein Interacting Protein Interaktionspartner. Mouse (Murine) Aurora Kinase A and ... Top anti-Aurora Kinase A and Ninein Interacting Protein Antikörper auf antikoerper-online.de. Showing 10 out of 24 products:. ... Human Aurora Kinase A and Ninein Interacting Protein (AUNIP) Interaktionspartner * AIBp (zeige APOA1BP Antikörper) may not only ...
  • Aurora kinases are serine/threonine kinases that are essential for cell proliferation. (wikipedia.org)
  • Giet R, Prigent C. Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. (wikipedia.org)
  • Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene. (wikipedia.org)
  • Aurora A is a member of a family of mitotic serine/threonine kinases. (wikipedia.org)
  • The Aurora family of serine/threonine kinases is essential for mitosis. (rcsb.org)
  • Aurora A and Aurora B are structurally related serine/threonine protein kinases that function during mitosis. (pnas.org)
  • 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 pipeline Target constitutes close to 16 molecules. (pharmiweb.com)
  • Aurora kinases are a highly conserved family of enzymes which add phospho-groups to Serine/Threonine residues of substrate proteins functioning in chromatid segregation during cell division. (biovision.com)
  • 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)
  • AURKA (Aurora Kinase A) belongs to the mitotic serine/threonine kinases family. (prospecbio.com)
  • Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. (eurekaselect.com)
  • Aurora-A is a serine-threonine kinase implicated in the assembly and maintenance of the mitotic spindle. (rupress.org)
  • Although these processes are diverse and executed by a cadre of functional classes of proteins, posttranslational protein phosphorylation by a small group of serine-threonine kinases orchestrates many aspects of most steps from mitotic entry to exit. (sciencemag.org)
  • Aurora Kinase 1 and 2 encode cell cycle-regulated serine/threonine kinases that are involved in microtubule spindle activities during mitosis and meiosis. (leicabiosystems.com)
  • Many epithelial cancers show cell cycle dysfunction tightly correlated with the overexpression of the serine/threonine kinase Aurora A (AURKA). (elifesciences.org)
  • The Aurora kinase family (EC is a collection of highly related serine/threonine kinases that functions as a key regulator of mitosis, essential for accurate and equal segregation of genomic material from parent to daughter cells. (axonmedchem.com)
  • Any of a family of three highly homologous serine/threonine kinases (Aurora kinase A, Aurora kinase B and Aurora kinase C), which play a critical role in regulating many processes that are pivotal to mitosis. (thefreedictionary.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 pipeline Target constitutes close to 13 molecules. (marketresearch.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 - Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that contributes to the regulation of cell cycle progression. (marketresearch.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 targeted therapeutics development with respective active and dormant or discontinued projects. (marketresearch.com)
  • 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 - Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. (researchmoz.us)
  • Furthermore, this report also reviews key players involved in 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 targeted therapeutics development with respective active and dormant or discontinued projects. (researchmoz.us)
  • Aurora A Kinase, along with -B and -C, are members of a family of serine/threonine protein kinases that play critical roles in coordinating mitosis, including establishment of the mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. (bellbrooklabs.com)
  • Aurora kinases are highly conserved serine/threonine kinases in eukaryotes, involved in many processes during cell division. (roche.com)
  • We have identified two human homologues of these genes, termed aurora1 and aurora2 , that encode cell‐cycle‐regulated serine/threonine kinases. (embopress.org)
  • The Aurora family members of serine/threonine kinases, Aurora A, B and C, play key roles in the regulation of cell division. (oncotarget.com)
  • This research project has focused on the Aurora kinases, a family of serine/threonine kinases which play a central role in chromosome segregation and cell division during mitosis. (ucl.ac.uk)
  • Aurora kinase family of serine/threonine kinases, frequently overexpressed in human cancers and implicated in tumorigenesis, induce chromosomal instability and oncogenic transformation when expressed at elevated levels in mammalian cells in vitro and in vivo. (elsevier.com)
  • 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). (bath.ac.uk)
  • Aurora kinase is an important class of serine/threonine kinases responsible for the regulation of cell mitosis. (creative-diagnostics.com)
  • Aurora 2) functions during prophase of mitosis and is required for correct duplication and separation 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)
  • 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)
  • Although Aurora B is regarded as the "master regulator" of kinetochore-microtubule attachment, other mitotic kinases likely contribute to Hec1 phosphorylation. (rupress.org)
  • In this study, we demonstrate that Aurora A kinase regulates kinetochore-microtubule dynamics of metaphase chromosomes, and we identify Hec1 S69, a previously uncharacterized phosphorylation target site in the Hec1 tail, as a critical Aurora A substrate for this regulation. (rupress.org)
  • Nevertheless, the role of Aurora-dependent phosphorylation in establishing asymmetry might be conserved. (plantcell.org)
  • In many cases, these changes are brought about by reversible phosphorylation, and several protein kinases and phosphatases undergo at least transient association with either centrosomes or spindle MTs ( Nigg, 2001 ). (rupress.org)
  • Activation of Aurora A can impinge on YAP activity through direct phosphorylation. (ovid.com)
  • To discover more about the functions of Aurora A, Aurora B, and kinases of the Plk family, we mapped mitotic phosphorylation sites to these kinases through the combined use of quantitative phosphoproteomics and selective targeting of kinase activities by small-molecule inhibitors. (sciencemag.org)
  • CCT137690 efficiently inhibits histone H3 and TACC3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. (aacrjournals.org)
  • Aurora Kinase 2 is regulated by phosphorylation which is important both for its activity and stability. (leicabiosystems.com)
  • 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. (sciencemag.org)
  • Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules. (sciencemag.org)
  • Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). (aacrjournals.org)
  • Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. (aacrjournals.org)
  • Prostate cancer cells expressing a S273A mutant of CHIP have attenuated AR degradation upon 2-ME treatment compared to cells expressing wild-type CHIP, supporting the idea that CHIP phosphorylation by Aurora A activates its E3 ligase activity for the AR. (aacrjournals.org)
  • Accumulated NIK converts c-Abl tyrosine kinase from a nuclear proapoptotic into a cytoplasmic antiapoptotic effector by inducing its phosphorylation at Thr735, Tyr245 and Tyr412 residues, and, by entering into a trimeric complex formation with c-Abl and STAT3, increases both the transcriptional activity of STAT3 and expression of the antiapoptotic STAT3 target genes PIM1 and PIM2. (haematologica.org)
  • Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53," Nature Genetics, vol. (thefreedictionary.com)
  • Live-cell imaging of a Forster resonance energy transfer (FRET)-based aurora kinase phosphorylation sensor revealed that midzone substrates were less phosphorylated in AAK-inhibited cells, despite the fact that midzone levels of active phosphorylated ABK (pABK) were normal. (thefreedictionary.com)
  • In human cancer cells, these dual inhibitors block the auto-phosphorylation of Aurora A (Thr-288) and the phosphorylation of the Aurora B substrate histone H3 (Ser-10) and the JAK2 substrate STAT3 (Tyr-705). (oncotarget.com)
  • Protein kinases are activated by phosphorylation and by the binding of activator proteins. (bath.ac.uk)
  • Based on this analysis, we propose a revised, fluid model of Aurora-A activation in which the first step is a reduction in the mobility of the activation loop by either TPX2 binding or phosphorylation. (bath.ac.uk)
  • Furthermore, our results suggest that unphosphorylated Aurora-A bound to the mitotic spindle by TPX2 is catalytically active and that the phosphorylation state of Aurora-A is an inaccurate surrogate for its activity. (bath.ac.uk)
  • Comparison with other kinases showed that kinetic characterization detects those kinases whose activation loops undergo a rearrangement upon phosphorylation and thus whose unphosphorylated state offers a distinct target for the development of Type II inhibitors. (bath.ac.uk)
  • Dodson, C & Bayliss, R 2012, ' Activation of Aurora-A Kinase by Protein Partner Binding and Phosphorylation Are Independent and Synergistic ', Journal of Biological Chemistry , vol. 287, pp. 1150-1157. (bath.ac.uk)
  • This process relies largely on increased phosphorylation of kinetochore substrates of Aurora B kinase at misaligned versus aligned kinetochores. (elsevier.com)
  • Current models explain this differential phosphorylation by spatial changes in the position of substrates relative to a constant pool of kinase at the inner centromere. (elsevier.com)
  • Aurora B is enriched at misaligned centromeres in these cells, and the dynamic range of Aurora B substrate phosphorylation at misaligned versus aligned kinetochores is increased. (elsevier.com)
  • Our results suggest a feedback mechanism in which Aurora B both regulates and is regulated by chromosome attachment to the spindle, which amplifies the differential phosphorylation of kinetochore substrates and increases the efficiency of error correction. (elsevier.com)
  • Like any kinase, Auroras function via the phosphorylation of their substrates. (ugent.be)
  • Preliminary evidence indicates that the animal aurora kinase phosphorylation motif is at least partially conserved in plant substrates of aurora kinases. (ugent.be)
  • Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression. (ugent.be)
  • Aurora kinase A (AURKA) plays a vital role in several cancers, but little is known about its role in bladder cancer. (urotoday.com)
  • The human aurora kinase family comprises three members: Aurora A, B and C (AURKA, AURKB and AURKC). (biovision.com)
  • AURKA is a cell cycle-regulated kinase which may be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. (prospecbio.com)
  • AIBp (zeige APOA1BP Antikörper ) may not only be required for the dynamic movement of Aurora-A (zeige AURKA Antikörper ) at the centrosomes and spindle apparatus during the cell cycle, but may also be important during brain tumorigenesis. (antikoerper-online.de)
  • Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. (lu.se)
  • Aurora Kinase 2, also known as AurkA, STK15, BTAK, ARK1 and AIK1, localizes to interphase and mitotic centrosomes and to the spindle poles. (leicabiosystems.com)
  • Also In May, the drug giant made another acquisition to strengthen its cancer franchise by announcing an agreement to acquire AurKa Pharma, a company established by TVM Capital Life Science to develop oncology compound AK-01, an Aurora kinase A inhibitor that was originally discovered at Lilly. (thefreedictionary.com)
  • AurKa Pharma was established as part of the TVM Life Science Ventures VII fund, to develop an Aurora kinase A inhibitor called AK-01, an oncology compound that was originally discovered through a Lilly research and development program. (thefreedictionary.com)
  • AurKa Pharma is a company established by investment advisory and fund managers group TVM Capital Life Science to develop oncology compound AK-01, an Aurora kinase A inhibitor that was originally discovered at Lilly. (thefreedictionary.com)
  • In a recent study of 25 prostatic adenocarcinomas with Paneth cell-like neuroendocrine differentiation, 45% showed amplification of the Aurora Kinase A (AURKA) gene, which was associated with a higher percentage of Paneth cell-like neuroendocrine differentiation throughout the tumor, ductal features and a higher Gleason score. (thefreedictionary.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 human Aurora kinases present a similar domain organization, with a N-terminal domain of 39-129 residues in length, a related Ser/Thr protein kinase domain and a short C-terminal domain containing 15-20 residues. (wikipedia.org)
  • In keeping with many protein kinase inhibitors, this compound is not a monospecific agent, and its cellular specificity remains largely unknown. (nih.gov)
  • Kimura, Matsuda, Yoshioka, Okano: Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. (antikoerper-online.de)
  • Danu induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (Erk1/2) and inhibited the activation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in breast cancer cells. (dovepress.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)
  • 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. (nih.gov)
  • 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 A regulates chromosome maturation and mitotic spindle formation, Aurora B controls chromosomal segregation and cytokinesis [ 1 , 2 ] whereas Aurora C is involved in meiosis [ 3 ]. (oncotarget.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)
  • The kinases Aurora-A, -B and -C represent a family of such targets and several small-molecule inhibitors have been shown to block their function. (nih.gov)
  • Taken together, these data identify Aurora A and Aurora B as dual intracellular targets of VX-680. (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)
  • Aurora A and B overexpression has also been associated with various human cancers and as such, they have been extensively studied as novel anti-mitotic drug targets. (aacrjournals.org)
  • Although a number of mitotic kinases have been identified, their targets and the intricacies of mitotic signal transduction pathways are just beginning to be understood. (asm.org)
  • 3] Aurora Kinases: New Targets for Cancer Therapy. (axonmedchem.com)
  • Thus, the combined data provide new information on host cell kinases involved in viral replication and uncovered potential targets for future antiviral strategies. (ovid.com)
  • The implication of the auroras in tumourigenesis and the fact that that they are kinases, amenable to small molecule inhibition, makes them attractive targets for anticancer drug development. (biomedcentral.com)
  • The Aurora kinases regulate multiple aspects of mitotic progression, and their overexpression in diverse tumor types makes them appealing oncology targets. (semanticscholar.org)
  • The compound also targets Aurora A kinase and tubulin in vitro and in cells, which can explain the observed spindle anomalies. (oup.com)
  • Therefore, these kinases are highly sought after as targets for the discovery of new anticancer drugs and intense efforts have been made to prepare specific pharmacological inhibitors [ 10 ]. (oncotarget.com)
  • As a result, Aurora-A and -B are being investigated as potential targets for cancer therapy and multiple agents targeting the kinases are in early phase clinical trials with some having yielded encouraging results. (elsevier.com)
  • This chapter discusses functional involvement of Aurora kinase-A and -B in the regulation of cell proliferation and cancer-relevant cellular pathways validating their significance as cancer therapeutic targets. (elsevier.com)
  • MLN8054 is a selective small-molecule Aurora A kinase inhibitor that has entered Phase I clinical trials for advanced solid tumors. (pnas.org)
  • Inactivating mutations in Aurora A or targeted protein depletion in cells derived from Drosophila melanogaster , Xenopus laveis , Caenorhabditis elegans , and human tumors prevent centrosome maturation, resulting in improper formation of the mitotic spindle ( 5 - 9 ). (pnas.org)
  • Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. (aacrjournals.org)
  • 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)
  • 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)
  • Inhibition of both MEK and Aurora kinase in KRAS-mutant tumors was observed when BI 847325 was administered once weekly at 70 mg/kg. (aacrjournals.org)
  • To understand the molecular and cellular events involved in solely estrogen-induced oncogenesis, we studied the role of mitotic kinases, Aurora A and B, and the MDM2-p53wt pathway in estrogen-elicited oncogenesis, using two animal tumor models, the estrogen-induced tumors of the kidney in male Syrian hamsters, and the mammary gland in female ACI rats. (ku.edu)
  • Alisertib (MLN8237) is an investigational, orally available, selective Aurora A kinase inhibitor in clinical development for the treatment of solid tumors and hematological malignancies. (aspetjournals.org)
  • The VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers. (escholarship.org)
  • Aurora A, B and C kinases are found overexpressed in solid tumors, including colorectal, breast, and ovarian as well as leukemia [ 4 , 5 ]. (oncotarget.com)
  • Inhibition of Aurora B in mammalian cells prevents proper alignment of chromosomes to the spindle plate, inhibits cytokinesis, and results in the formation of multinucleated cells ( 15 - 18 ). (pnas.org)
  • Aurora-like kinases play key roles in chromosome segregation and cytokinesis in yeast, plant, and animal systems. (uniprot.org)
  • Complementation assays showed that the Arabidopsis α group Aurora kinases are functionally divergent from the single β group member AUR3 and that AUR1 functions in division plane orientation prior to cytokinesis. (plantcell.org)
  • Aurora A is required for spindle formation while aurora B is required for chromosome condensation and cytokinesis. (biologists.org)
  • Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. (biomedcentral.com)
  • Aurora-A is frequently overexpressed in cancers, and its dysregulation is believed to drive tumorigenesis by causing chromosomal instability and tumor cell heterogeneity 2,3 Research on abnormal Aurora A kinase levels have shown centrosome amplification, aneuploidy from failure in cytokinesis, and cell transformation in cases of over-expression which can be linked to carcinogenesis and tumorigenesis. (bellbrooklabs.com)
  • Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
  • In cytokinesis, Aurora B further aggregates into the intermediate. (creative-diagnostics.com)
  • 2005). Whereas the Beta type Aurora of Arabidopsis localizes to centromeric regions, both Alpha type Auroras associate with the prophase spindle, kinetochore fibers during metaphase and anaphase and accumulate at the forming cell plate during cytokinesis, both in tobacco BY-2 cells as in Arabidopsis root cells. (ugent.be)
  • The transcripts and proteins of all three kinases are most abundant in tissues containing dividing cells. (uniprot.org)
  • The interaction with certain proteins not only contributes to kinase activation but also governs the spatially and temporally distinct subcellular localization of the three family members. (sciencemag.org)
  • Though the first Aurora kinase inhibitor, alisertib, entered the clinic several years ago, success has been limited possibly because of inhibition of Aurora B and C as well as off-target effects on unrelated proteins. (bellbrooklabs.com)
  • Synthetic peptide near the C-terminus of human Aurora kinase A, B, and C proteins. (roche.com)
  • Purpose Review aberrations of insulin signaling to atypical proteins kinase C (aPKC) in muscles and liver that generate cardiovascular risk elements, including, weight problems, hypertriglyceridemia, hypercholesterolemia, insulin level of resistance and blood sugar intolerance in type 2 diabetes mellitus (T2DM), and obesity-associated metabolic symptoms (MetSyn). (biomasswars.com)
  • as well as the downstream molecule extracellular indication regulated proteins kinase (ERK) 1/2, which induced the upregulation of p53 and Bcl-2-linked X proteins, mediating the next mobile apoptosis and proliferation in IECs. (biomasswars.com)
  • Aurora B can regulate this process by acting on checkpoint proteins (Mps1, Mad, Bud). (creative-diagnostics.com)
  • VX-680, also known as MK-0457, is a member of a diverse group of small molecules that inhibit the Aurora kinases, and has shown significant potential as an anti-cancer agent. (nih.gov)
  • Although these molecules were found to inhibit both Aurora A and Aurora B protein kinases in vitro , the major cellular phenotypic response they produced was consistent with inhibition of Aurora B ( 15 , 18 , 21 - 24 ). (pnas.org)
  • 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)
  • Importantly, we have developed dual Aurora and JAK inhibitors, AJI-214 and AJI-100, which potently inhibit Aurora A, Aurora B and JAK2 in vitro. (oncotarget.com)
  • Destabilization of incorrect attachments requires the Ipl1/Aurora B kinase, which phosphorylates kinetochore substrates that directly interact with microtubules. (nih.gov)
  • Central to this regulation is Aurora B kinase, which phosphorylates kinetochore substrates to promote microtubule turnover. (rupress.org)
  • Aurora A is able to phosphorylate diverse substrates, making it vital in regulating spindle fiber alignment of chromosomes in anaphase for normal centrosome separation. (bellbrooklabs.com)
  • To investigate the causality of the aberrant division plane orientations, we are hunting for aurora kinase substrates. (ugent.be)
  • 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)
  • Inhibitors of aurora kinases were shown to induce apoptosis in vitro and in vivo. (nih.gov)
  • We report herein the discovery and optimization of a novel series of tricyclic molecules that has led to SAR156497, an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy. (rcsb.org)
  • MLN8054 inhibits recombinant Aurora A kinase activity in vitro and is selective for Aurora A over the family member Aurora B in cultured cells. (pnas.org)
  • Doyle, Lee, Selesniemi, Styer, Rueda: The impact of vitrification on murine germinal vesicle oocyte In vitro maturation and aurora kinase A protein expression. (antikoerper-online.de)
  • MLN8054 is an ATP-competitive, reversible inhibitor of recombinant Aurora A kinase with an IC50 of 4 nM, which shows >40-fold more selective inhibitory activity for Aurora A compared with Aurora B. [1] In vitro, MLN8054 exhibits the activity of growth inhibition across various cell lines from diverse tissue origins with IC50 values ranging from 0.11 μM to 1.43 μM. (selleckchem.com)
  • An in vitro kinase assay demonstrated that AtAurora1 preferentially phosphorylates histone H3 at Ser 10 but not at Ser 28 or Thr 3, 11, and 32. (uniprot.org)
  • These results indicate that murine Aurora-A facilitates, but is not absolutely required for, mitotic entry in murine embryonic fibroblasts and is essential for centrosome separation and bipolar spindle formation in vitro and in vivo. (asm.org)
  • The premature termination of M phase was found to be a consequence of precocious inactivation of SAC caused by a direct inhibitory effect of the compound on Aurora B kinase in vitro and in cells. (oup.com)
  • Millennium said it believes that inhibition of Aurora kinase causes anomalies to occur during cell division, leading to apoptosis. (bioworld.com)
  • Aurora A Activity is positively-regulated by the spindle protein TPX2, and has recently been shown to be a target for thiol-containing molecules, such as Coenzyme A. Aurora B (a.k.a. (wikipedia.org)
  • Aurora 1) functions in the attachment of the mitotic spindle to the centromere. (wikipedia.org)
  • As the cell cycle progresses, concentrations of Aurora A increase and the kinase associates with the mitotic poles and the adjacent spindle microtubules. (wikipedia.org)
  • Right before mitotic exit, Aurora A relocalizes to the mid-zone of the spindle. (wikipedia.org)
  • Aurora A is critical for proper formation of mitotic spindle. (wikipedia.org)
  • Furthermore, Aurora A is necessary for the proper separation of the centrosomes after the mitotic spindle has been formed. (wikipedia.org)
  • Without Aurora A, the mitotic spindle, depending on the organism, will either never separate or will begin to separate only to collapse back onto itself. (wikipedia.org)
  • A recent study has shown that one of these dual inhibitors also produces a phenotype consistent with Aurora A kinase inhibition, namely mitotic spindle abnormalities ( 27 ). (pnas.org)
  • Aurora A is important in centrosome function and duplication, mitotic entry and bipolar spindle assembly. (biovision.com)
  • In addition, MLN8054 selectively inhibits Aurora A over Aurora B in cultured cells, and inhibits cell proliferation by promoting G2/M accumulation and spindle defects in multiple cultured human tumor cells lines. (selleckchem.com)
  • Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus. (rupress.org)
  • Binding studies demonstrated that the NH 2 terminus of TPX2 can directly interact with the COOH-terminal catalytic domain of Aurora-A. Although kinase activity was not required for this interaction, TPX2 was readily phosphorylated by Aurora-A. Upon siRNA-mediated elimination of TPX2 from cells, the association of Aurora-A with the spindle microtubules was abolished, although its association with spindle poles was unaffected. (rupress.org)
  • In turn, Aurora-A might regulate the function of TPX2 during spindle assembly. (rupress.org)
  • Aurora A has been implicated in the G 2 -M transition ( 5 - 9 ), centrosome maturation and separation, as well as the formation of a bipolar spindle ( 4 ). (sciencemag.org)
  • Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. (sciencemag.org)
  • Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. (asm.org)
  • We show here that conditional Aurora-A ablation in cultured embryonic fibroblasts causes impaired mitotic entry and mitotic arrest with a profound defect in bipolar spindle formation. (asm.org)
  • Germ line Aurora-A deficiency causes embryonic death at the blastocyst stage with pronounced cell proliferation failure, mitotic arrest, and monopolar spindle formation. (asm.org)
  • Aurora-A kinases are observed at centrosomes and adjacent spindle fibers, and current evidence supports key roles in regulating protein localization and function at centrosomes, as well as regulation of the assembly, stability, and function of the mitotic spindle (reviewed in reference 43 ). (asm.org)
  • Aurora A and Aurora B kinases are implicated in regulation of spindle assembly and correction of chromosomal segregation. (thefreedictionary.com)
  • Consistent with its role in spindle formation, aurora A kinase associates with the centrosome and microtubules. (biologists.org)
  • Aurora kinase was first discovered in Drosophila mutants and was named for its abnormal spindle morphology like the Northern Lights. (creative-diagnostics.com)
  • In addition, Aurora A is also distributed on the spindle microtubes. (creative-diagnostics.com)
  • Deletion of Aurora-A or inhibition of its activity can cause centrosome separation failure, which ultimately leads to the appearance of a monopolar spindle. (creative-diagnostics.com)
  • In mammalian cells, interference with Aurora A or TPX2 can cause the formation of a multipolar spindle, indicating that the interaction of TPX2 with Aurora A is a necessary condition for the formation of a bipolar spindle. (creative-diagnostics.com)
  • In addition to its role in centrosome separation, maturation, and spindle assembly, Aurora A also promotes cell entry into the dividing phase via Cyclin-B/Cdk1. (creative-diagnostics.com)
  • After splitting into the late stage, Aurora B migrates from the centromere to the middle region of the central spindle and the cell cortex of the dividing groove. (creative-diagnostics.com)
  • Danu arrested MCF7 and MDA-MB-231 cells in G 2 /M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. (dovepress.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)
  • 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)
  • Furthermore, siRNA silencing or pharmacological inhibition of Aurora A and JAK2 with Alisertib and Ruxolitinib, respectively, is more effective than blocking each kinase alone at suppressing anchorage-dependent and -independent growth and invasion as well as at inducing apoptosis. (oncotarget.com)
  • The Aurora A gene is amplified and overexpressed in cancers originating from multiple tissue types ( 19 ). (pnas.org)
  • Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. (aacrjournals.org)
  • Structure and expression of AtAurora1 and AtAurora2 suggest that these genes arose by a recent gene duplication, whereas the diversification of plant alpha and beta Aurora kinases predates the origin of land plants. (uniprot.org)
  • Relevant molecular alterations encountered in thyroid cancer progression comprise gene rearrangements of tyrosine kinase receptors, such as the RET/PTC and NTRK1, activating point mutations of the RAS and BRAF genes, and the oncogenic fusion protein PAX8-PPARγ [ 7 ]. (plos.org)
  • A gene on chromosome 17p13.1 that encodes Aurora kinase B, which is involved in regulating many mitotic events. (thefreedictionary.com)
  • We developed a conditional null mutation in the mouse Aurora-A gene to investigate Aurora-A functions in primary cells ex vivo and in vivo. (asm.org)
  • Deregulation of Aurora kinase gene expression in human testicular germ cell tumours. (thefreedictionary.com)
  • In contrast, inhibition of Aurora A kinase promoted an enhancement of viral early-late gene expression, suggesting a putative role of Aurora A signaling in host defense. (ovid.com)
  • Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1. (uniprot.org)
  • In general, we found that TRAP220/MED1 expression is required for high basal levels of Aurora-A gene expression and that ectopic overexpression of TRAP220/MED1 coactivates transcription from the Aurora-A gene promoter. (uniprot.org)
  • Finally, we present evidence suggesting that TRAP/Mediator is recruited to the Aurora-A gene via direct interactions between TRAP220/MED1 and the Ets-related transcription factor GABP. (uniprot.org)
  • The aurora a gene is located on chromosome 20q13. (creative-diagnostics.com)
  • The coding gene of Aurora B is located on chromosome 17p13. (creative-diagnostics.com)
  • Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237. (semanticscholar.org)
  • Aurora-B is the catalytic component of the chromosomal passenger complex (CPC), which is composed of three additional non-catalytic subunits that direct its activity: survivin, inner centromere protein (INCENP) and borealin. (biomedcentral.com)
  • These findings indicate that in addition to Aurora B regulating kinetochore- microtubule binding, the kinetochore also controls Aurora B recruitment to the inner centromere. (elsevier.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)
  • 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)
  • 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)
  • Aurora-A deletion increases apoptosis, suggesting that molecular therapies targeting Aurora-A may be effective in inducing tumor cell apoptosis. (asm.org)
  • 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)
  • 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)
  • 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)
  • They are strongly linked to cancer progression, and while overexpression of Aurora A and B occurs in many cancers, neither is regarded as an oncoprotein (as oncogenic mutations are required to promote tumour progression). (thefreedictionary.com)
  • 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)
  • Three Aurora kinases have been identified in mammalian cells to date. (wikipedia.org)
  • Aurora Kinase 2 overexpression leads to centrosome amplification, chromosome instability and transformation in mammalian cells. (leicabiosystems.com)
  • Members of the aurora kinase family regulate a range of mitotic processes. (biologists.org)
  • The Aurora family includes a single member in yeasts ( Saccharomyces cerevisiae Ipl1p, Schizosaccharomyces pombe Ark1), two members each in Caenorhabditis elegans and Drosophila , and two or three members in vertebrates. (asm.org)
  • These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. (embopress.org)
  • Aurora A has been shown to be essential for centrosome maturation in nematodes, fruit flies, and human cells. (creative-diagnostics.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)
  • 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)
  • 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)
  • VX-680 inhibits Aurora A and Aurora B kinase activity in human cells. (nih.gov)
  • 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)
  • Here we characterise the Aurora kinase inhibitor CCT137690, a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinases with low nanomolar IC50 values in both biochemical and cellular assays and exhibits anti-proliferative activity against a wide range of human solid tumour cell lines. (aacrjournals.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)
  • Myeloma-cell samples with detectable vs. absent Aurora-A expression show a significantly higher proliferation rate, but neither a higher absolute number of chromosomal aberrations present (aneuploidy) nor of subclonal aberrations (chromosomal instability). (archives-ouvertes.fr)
  • Danusertib (Danu) is a pan-inhibitor of Aurora kinases and a third-generation breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (Bcr-Abl) tyrosine kinase inhibitor, but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. (dovepress.com)
  • Completing the structural family portrait of the human EphB tyrosine kinase domains. (semanticscholar.org)
  • Overexpression of both active and inactive Aurora Kinase 2 can lead to polyploidy. (leicabiosystems.com)
  • A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. (plos.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)
  • 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)
  • A cell-permeable anilinoquinazoline compound that acts as a potent, selective, and ATP-competitive inhibitor of Aurora kinases (IC 50 = 310 nM and 240 nM for Aurora A and B, respectively, 1.25 µM in MCF7 cells). (merckmillipore.com)
  • A cell-permeable, potent, selective, and ATP-competitive inhibitor of Aurora kinases (IC 50 = 310 nM and 240 nM for Aurora A and B, respectively, 1.25 µM in MCF7 cells). (merckmillipore.com)
  • Maleic acid is used in the synthesis of pyridoindolones as potent inhibitors of Aurora kinases. (csnpharm.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)
  • Over-expression of Aurora kinases is reported to be associated with genetic instability and tumor formation [ 6 ] and several lines of evidence implicate Aurora kinases in malignant transformation [ 7 - 9 ]. (oncotarget.com)
  • ZM447439 (ZM) is a potent and selective inhibitor of aurora-A and -B kinase with putative anti-tumoral activity. (nih.gov)
  • VX-680 also exhibits potent cytotoxicity when compared to the well documented Aurora B inhibitor ZM447439. (nih.gov)
  • MLN8054, a Potent and Selective Inhibitor of Aurora A Kinase Activity. (pnas.org)
  • MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. (selleckchem.com)
  • Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 was demonstrated in enzymatic and cellular assays. (aacrjournals.org)
  • A cell-permeable 2,4-dianilinopyrimidine compound that acts as an ATP-competitive, potent, but non-selective inhibitor of Aurora A (IC 50 = 42 nM). (emdmillipore.com)
  • What have these studies taught us about the therapeutic potential of inhibiting this family of kinases? (nih.gov)
  • 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)
  • 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)
  • 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)
  • Genetic instability and cellular proliferation have been associated with Aurora-kinase expression in several cancer entities, including multiple myeloma. (archives-ouvertes.fr)
  • 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)
  • 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)
  • The Aurora kinase inhibitors in cancer research and therapy. (thefreedictionary.com)
  • The reduced activity of Aurora B kinase resulted in polyploidy and suppression of cancer cell viability. (oup.com)
  • 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)
  • Perturbation of Aurora kinase expression or function might lead to cancer. (ed.ac.uk)
  • 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)
  • 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)
  • More specifically, Aurora kinases play a crucial role in cellular division by controlling chromatid segregation. (wikipedia.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)
  • 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)
  • It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD. (thefreedictionary.com)
  • Aurora A and JAK2 kinases are involved in cell division and tumor cell survival, respectively. (oncotarget.com)
  • Here we demonstrate that ectopic expression of Aurora A and JAK2 together is more effective than each alone at inducing non-transformed cells to grow in an anchorage-independent manner and to invade. (oncotarget.com)
  • Taken together, our genetic and pharmacological studies indicate that targeting Aurora A and JAK2 together is a more effective approach than each kinase alone at inhibiting malignant transformation and warrant further advanced pre clinical investigations of dual Aurora A/JAK2 inhibitors as potential anti tumor agents. (oncotarget.com)
  • The aurora kinases were first identified in 1990 during a cDNA screen of Xenopus eggs. (wikipedia.org)
  • In the case of the former, it has been suggested that Aurora A cooperates with the kinase Nek2 in Xenopus to dissolve the structure tethering the cell's centrosomes together. (wikipedia.org)
  • Identification of a functional destruction box in the Xenopus laevis aurora-A kinase pEg2. (inserm.fr)
  • Here, we characterize three Arabidopsis thaliana protein kinases, designated AtAurora1, AtAurora2, and AtAurora3, which share high amino acid identities with the Ser/Thr kinase domain of yeast Ipl1 and animal Auroras. (uniprot.org)
  • 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)
  • 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)
  • In the absence of Aurora A mad2, a protein that normally dissipates once a proper kinetochore-microtubule connection is made, remains present even into metaphase. (wikipedia.org)