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.
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.
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.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
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.
Seven membered heterocyclic rings containing a NITROGEN atom.
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.
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.
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.
BENZOIC ACID amides.
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.
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 cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
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 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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
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.
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.
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.
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)
Agents which affect CELL DIVISION and the MITOTIC SPINDLE APPARATUS resulting in the loss or gain of whole CHROMOSOMES, thereby inducing an ANEUPLOIDY.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
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.
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.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
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.
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.
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.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
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.
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.
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.
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).
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
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.
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.
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 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).
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.

Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. (1/454)

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

The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. (2/454)

Baculoviral IAP repeat proteins (BIRPs) may affect cell death, cell division, and tumorigenesis. The C. elegans BIRP BIR-1 was localized to chromosomes and to the spindle midzone. Embryos and fertilized oocytes lacking BIR-1 had defects in chromosome behavior, spindle midzone formation, and cytokinesis. We observed indistinguishable defects in fertilized oocytes and embryos lacking the Aurora-like kinase AIR-2. AIR-2 was not present on chromosomes in the absence of BIR-1. Histone H3 phosphorylation and HCP-1 staining, which marks kinetochores, were reduced in the absence of either BIR-1 or AIR-2. We propose that BIR-1 localizes AIR-2 to chromosomes and perhaps to the spindle midzone, where AIR-2 phosphorylates proteins that affect chromosome behavior and spindle midzone organization. The human BIRP survivin, which is upregulated in tumors, could partially substitute for BIR-1 in C. elegans. Deregulation of bir-1 promotes changes in ploidy, suggesting that similar deregulation of mammalian BIRPs may contribute to tumorigenesis.  (+info)

The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is required for cytokinesis. (3/454)

BACKGROUND: The Aurora/Ipl1p-related kinase AIR-2 is required for mitotic chromosome segregation and cytokinesis in early Caenorhabditis elegans embryos. Previous studies have relied on non-conditional mutations or RNA-mediated interference (RNAi) to inactivate AIR-2. It has therefore not been possible to determine whether AIR-2 functions directly in cytokinesis or if the cleavage defect results indirectly from the failure to segregate DNA. One intriguing hypothesis is that AIR-2 acts to localize the mitotic kinesin-like protein ZEN-4 (also known as CeMKLP1), which later functions in cytokinesis. RESULTS: Using conditional alleles, we established that AIR-2 is required at metaphase or early anaphase for normal segregation of chromosomes, localization of ZEN-4, and cytokinesis. ZEN-4 is first required late in cytokinesis, and also functions to maintain cell separation through much of the subsequent interphase. DNA segregation defects alone were not sufficient to disrupt cytokinesis in other mutants, suggesting that AIR-2 acts specifically during cytokinesis through ZEN-4. AIR-2 and ZEN-4 shared similar genetic interactions with the formin homology (FH) protein CYK-1, suggesting that AIR-2 and ZEN-4 function in a single pathway, in parallel to a contractile ring pathway that includes CYK-1. Using in vitro co-immunoprecipitation experiments, we found that AIR-2 and ZEN-4 interact directly. CONCLUSIONS: AIR-2 has two functions during mitosis: one in chromosome segregation, and a second, independent function in cytokinesis through ZEN-4. AIR-2 and ZEN-4 may act in parallel to a second pathway that includes CYK-1.  (+info)

Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. (4/454)

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)

Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. (5/454)

We have performed a biochemical and double-stranded RNA-mediated interference (RNAi) analysis of the role of two chromosomal passenger proteins, inner centromere protein (INCENP) and aurora B kinase, in cultured cells of Drosophila melanogaster. INCENP and aurora B function is tightly interlinked. The two proteins bind to each other in vitro, and DmINCENP is required for DmAurora B to localize properly in mitosis and function as a histone H3 kinase. DmAurora B is required for DmINCENP accumulation at centromeres and transfer to the spindle at anaphase. RNAi for either protein dramatically inhibited the ability of cells to achieve a normal metaphase chromosome alignment. Cells were not blocked in mitosis, however, and entered an aberrant anaphase characterized by defects in sister kinetochore disjunction and the presence of large amounts of amorphous lagging chromatin. Anaphase A chromosome movement appeared to be normal, however cytokinesis often failed. DmINCENP and DmAurora B are not required for the correct localization of the kinesin-like protein Pavarotti (ZEN-4/CHO1/MKLP1) to the midbody at telophase. These experiments reveal that INCENP is required for aurora B kinase function and confirm that the chromosomal passengers have essential roles in mitosis.  (+info)

INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. (6/454)

Three lines of investigation have suggested that interactions between Survivin and the chromosomal passenger proteins INCENP and Aurora-B kinase may be important for mitotic progression. First, interference with the function of Survivin/BIR1, INCENP, or Aurora-B kinase leads to similar defects in mitosis and cytokinesis [1-7] (see [8] for review). Second, INCENP and Aurora-B exist in a complex in Xenopus eggs [9] and in mammalian cultured cells [7]. Third, interference with Survivin or INCENP function causes Aurora-B kinase to be mislocalized in mitosis in both C. elegans and vertebrates [5, 7, 9]. Here, we provide evidence that Survivin, Aurora-B, and INCENP interact physically and functionally. Direct visualization of Survivin-GFP in mitotic cells reveals that it localizes identically to INCENP and Aurora-B. Survivin binds directly to both Aurora-B and INCENP in yeast two-hybrid and in vitro pull-down assays. The in vitro interaction between Survivin and Aurora-B is extraordinarily stable in that it resists 3 M NaCl. Finally, Survivin and INCENP interact functionally in vivo; in cells in which INCENP localization is disrupted, Survivin adheres to the chromosomes and no longer concentrates at the centromeres or transfers to the anaphase spindle midzone. Our data provide the first biochemical evidence that Survivin can interact directly with members of the chromosomal passenger complex.  (+info)

CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. (7/454)

Aurora B is a mitotic protein kinase that phosphorylates histone H3, behaves as a chromosomal passenger protein, and functions in cytokinesis. We investigated a role for Aurora B with respect to human centromere protein A (CENP-A), a centromeric histone H3 homologue. Aurora B concentrates at centromeres in early G2, associates with histone H3 and centromeres at the times when histone H3 and CENP-A are phosphorylated, and phosphorylates histone H3 and CENP-A in vitro at a similar target serine residue. Dominant negative phosphorylation site mutants of CENP-A result in a delay at the terminal stage of cytokinesis (cell separation). The only molecular defects detected in analysis of 22 chromosomal, spindle, and regulatory proteins were disruptions in localization of inner centromere protein (INCENP), Aurora B, and a putative partner phosphatase, PP1gamma1. Our data support a model where CENP-A phosphorylation is involved in regulating Aurora B, INCENP, and PP1gamma1 targeting within the cell. These experiments identify an unexpected role for the kinetochore in regulation of cytokinesis.  (+info)

Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. (8/454)

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)

Chromosome attachments to the mitotic spindle are regulated by tension across the centromere, which ensures accurate chromosome segregation. Spindle microtubules can bind chromosomes at the kinetochore in different configurations, but only bi-oriented attachments can support accurate chromosome segregation. Tension across the centromere distinguishes correct and incorrect attachments, but how tension is sensed to regulate attachments is unclear. The mitotic kinase Aurora B is a key regulator of kinetochore-microtubule attachments, and phosphorylation of Aurora B substrates at kinetochores reduces microtubule affinity. Liu et al. tested to see whether a tension-sensitive mechanism regulates Aurora B activity. Instead, their results suggest that Aurora B kinase activity is not directly regulated by tension but that phosphorylation of an Aurora B substrate at the kinetochore depends on its distance from the kinase at the inner centromere and that it is this distance that is affected by ...
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 ...
Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC). Localization of the CPC to the inner centromere is central to the current model for ho …
Mller (Reviews, 27 Oct 2006, p. yielding monopolar spindles or bipolar spindles missing centrosomes, in keeping with earlier observations (7,8). Therefore delays mitotic development inside a SAC-dependent way. The simplest description for SAC activation is usually that inhibition of -TuRC induces spindle problems that prevent kinetochores from attaining complete MT occupancy and/or arriving under tension. Nevertheless, the writers argue that simple explanation isnt sufficient to describe their observations, saying that -TuRCCdeficient cells display abundant microtubule arrays with amphitelic-like chromosome micro-tubule connection. Rather, they hypothesize that -tubulin is usually a part of a signaling complicated that creates the SAC when -TuRC protein are abrogated. SAC activation in -TuRCCdeficient cells argues against the hypothesis that -tubulin can be an activator from the SAC, although inside a formal feeling, -TuRC proteins become negative regulators from the SAC, as will additionally ...
Rhabdomyosarcoma is a primitive neoplasm with a poorly understood etiology that exhibits features of fetal skeletal muscle. of both and PA-824 through promoter and manifestation analyses suggested that increased resistance to apoptosis was associated with the inhibition of the Wnt signaling pathway. These results suggest that altered AP-1 activity that leads to PA-824 the down-regulation of the Wnt pathway may contribute to the inhibition of myogenic differentiation and resistance to apoptosis in ERMS cases. Efforts to unravel the molecular events underlying the origin of different types of cancer have contributed to obtaining treatments for these diseases. However, largely left behind in this effort are tumors with poorly comprehended etiologies like rhabdomyosarcoma (RMS). RMS explains a heterogeneous group of poorly differentiated pediatric sarcomas that display features of developing muscle.1 Representing 60% PA-824 of all pediatric sarcomas and accounting for 5% to 10% of all childhood ...
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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 ...
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This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes. [provided by RefSeq, Jul 2016 ...
Intrigued, Campbell and Desai began exploring how it had defied its predicted fate. As detailed in the current issue of Nature, what they discovered has overturned the prevailing model of how dividing cells ensure that each of their daughter cells emerge with equal numbers of chromosomes, which together package the genome. Getting the right number of chromosomes into each cell is absolutely essential to sustaining life, explains Desai, PhD, a Ludwig member at the University of California, San Diego, but it is also something that goes terribly wrong in cancer. The kinds of mistakes that occur when this process isnt functioning properly are seen in about 90% of cancers, and very frequently in advanced and drug-resistant tumors.. Campbell and Desais study focused in particular on four interacting proteins known as the chromosomal passenger complex (CPC) that monitor the appropriate parceling out of chromosomes. When cells initiate division, each chromosome is made of two connected, identical ...
The role of NF-κB as an apoptosis regulator provided a conceptual framework in which manipulation of NF-κB activity may serve as a drug target in different pathologic settings, including malignancy (3). Currently, there are several anti-NF-κB drugs being developed, primarily targeting the proteasome or IκB kinase activity (33). A common experimental approach to show the role of NF-κB in cell survival employs the expression of superrepressor IκBα or the use of NF-κB-deficient cells, such as p65 knockout mouse embryonic fibroblasts, to specifically attenuate NF-κB activity. In this study, we developed a NF-κB reporter cell system to positively examine the behavior of NF-κB-activated cells without prior manipulation of NF-κB activation potential. This system permitted the analysis of populational variations among drug- or radiation-exposed cells with respect to NF-κB activation, cell cycle regulation, and survival differences.. We found that activation of NF-κB occurred in different ...
Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase-dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT-MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of ...
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 ...
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 ...
Whether aurora A or aurora B is the better anticancer drug target is a matter of debate (8). At least two groups have directly addressed this question in the laboratory. Warner et al. (36) compared the effects of aurora A and aurora B antisense oligonucleotides in pancreatic cancer cells and found that aurora A-targeted therapy may be preferable to aurora B targeting, as shown by mitotic arrest and the rapid induction of apoptosis. Girdler et al. (37) compared the effects of RNA interference and small molecules targeting aurora A versus aurora B in colon cancer cells and found that the cells tested were extremely sensitive to aurora B inhibition. Interestingly, dual inhibition of aurora A and B results in phenotypes identical to inactivation of aurora B alone (28). Using RNA interference experiments, Yang et al. (38) showed that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy, indicating that aurora B is responsible for mitotic arrest in the absence ...
Whether aurora A or aurora B is the better anticancer drug target is a matter of debate (8). At least two groups have directly addressed this question in the laboratory. Warner et al. (36) compared the effects of aurora A and aurora B antisense oligonucleotides in pancreatic cancer cells and found that aurora A-targeted therapy may be preferable to aurora B targeting, as shown by mitotic arrest and the rapid induction of apoptosis. Girdler et al. (37) compared the effects of RNA interference and small molecules targeting aurora A versus aurora B in colon cancer cells and found that the cells tested were extremely sensitive to aurora B inhibition. Interestingly, dual inhibition of aurora A and B results in phenotypes identical to inactivation of aurora B alone (28). Using RNA interference experiments, Yang et al. (38) showed that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy, indicating that aurora B is responsible for mitotic arrest in the absence ...
Background: It is known that aurora B, a chromosomal passenger protein responsible for the proper progression of mitosis and cytokinesis, is overexpressed throughout the cell cycle in cancer cells. Overexpression of aurora B produced multinuclearity and induced aggressive metastasis, suggesting that overexpressed aurora B has multiple functions in cancer development. However, the detailed dynamics and functions of overexpressed aurora B are poorly understood. Results: We overexpressed GFP fused aurora B kinase in normal rat kidney epithelial cells. Using spinning disk confocal microscopy, we found that overexpressed aurora B-GFP was predominantly localized in the nucleus and along the cortex as a dot-like or short filamentous structure during interphase. Time-lapse imaging revealed that a cytoplasmic fraction of overexpressed aurora B-GFP was incorporated into the nucleus after cell division. Immunofluorescence showed that the nuclear fraction of overexpressed aurora B did not induce ectopic ...
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer-based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.. ...
Aurora B, the catalytic component of the chromosomal passenger complex (CPC), is an essential kinase in the error correction mechanism that ensures proper chromosome segregation when cells divide (8, 35). Reducing Aurora B activity by means of RNA interference or small-molecule inhibitors results in failure in chromosome alignment and defective kinetochore-microtubule attachment, cleavage furrow formation, and cytokinesis, ultimately leading to tetraploidization (36-39). Aurora B heterozygosity in the mouse results in increased tumor incidence, whereas complete loss of Aurkb prevents chromosome segregation and results in a premature mitotic exit (26, 34).. Although most studies have used loss-of-function approaches to understand the function of this kinase, Aurora B is overexpressed in many tumor types, and a correlation between its levels and tumor grade or poor clinical prognosis has been also proposed (16-18, 20-22). Previous cellular studies indicate that sustained overexpression of Aurora B ...
Aurora kinases play distinct roles during mitosis, with Aurora A being essential for centrosome maturation and spindle assembly and Aurora B functioning at kinetochores in chromosome attachment and at the end of mitosis in cytokinesis (reviewed in refs. 3, 4).. Inhibition of Aurora kinases is emerging as a new strategy for anticancer therapy, and several small-molecule inhibitors have entered clinical trials. In this report, we describe the biochemical and pharmacologic activity profile of PHA-739358, a spectrum-selective small-molecule kinase inhibitor, which was identified during a screen for inhibitors of Aurora kinases. In most of the cell lines tested, cells fail to divide, resulting in polyploidy without a strong impact on the timing of mitosis (data not shown) and finally leading to a reduction in viability. In some cell lines, an increased apoptosis was seen. This speaks for a dominant Aurora B kinase-related mechanism of action for inhibition because Aurora A inhibition would rather ...
Aurora kinases play distinct roles during mitosis, with Aurora A being essential for centrosome maturation and spindle assembly and Aurora B functioning at kinetochores in chromosome attachment and at the end of mitosis in cytokinesis (reviewed in refs. 3, 4).. Inhibition of Aurora kinases is emerging as a new strategy for anticancer therapy, and several small-molecule inhibitors have entered clinical trials. In this report, we describe the biochemical and pharmacologic activity profile of PHA-739358, a spectrum-selective small-molecule kinase inhibitor, which was identified during a screen for inhibitors of Aurora kinases. In most of the cell lines tested, cells fail to divide, resulting in polyploidy without a strong impact on the timing of mitosis (data not shown) and finally leading to a reduction in viability. In some cell lines, an increased apoptosis was seen. This speaks for a dominant Aurora B kinase-related mechanism of action for inhibition because Aurora A inhibition would rather ...
The condensin and chromosomal passenger complexes both have important roles in chromosome condensation in mitosis, and the passenger complex has been shown in many systems to be required for localization or phosphorylation of condensin proteins (Giet and Glover 2001; Morishita et al. 2001; Hagstrom et al. 2002; Kaitna et al. 2002; Lavoie et al. 2004; Lipp et al. 2007). Here we observe distinct meiotic consequences of mutations in dcap-g and incenp. Strikingly, SC disassembly was premature in incenp mutants but delayed in dcap-g mutants, and prometaphase I and metaphase I chromosome configurations were disrupted in both mutants, but in clearly distinguishable ways.. That both the condensin and passenger complexes affect SC disassembly is intriguing because little is known about regulation of this process. BubR1 has recently been shown to be required for SC maintenance (Malmanche et al. 2007), although the mechanism has not yet been established. A suggestion that condensin might be required for SC ...
BubR1 is a central component of the spindle assembly checkpoint (SAC) that inhibits progression into anaphase in response to improper kinetochore-microtubule interactions. In addition BubR1 also helps stabilize kinetochore-microtubule interactions by counteracting the Aurora B kinase but the mechanism behind this is not clear. Here we show that BubR1 directly binds to the B56 family of PP2A regulatory subunits through a conserved motif that is phosphorylated by Cdk1 and Plk1. Two highly conserved hydrophobic residues surrounding the S670 Cdk1 phosphorylation site are required for B56 binding and mutation of these residues prevents the establishment of a proper metaphase plate and delays cells in mitosis. Furthermore, we show that phosphorylation of S670 and S676 stimulates the binding of B56 to BubR1 and that BubR1 targets a pool of B56 to kinetochores. Our data suggests that BubR1 counteracts Aurora B kinase activity at improperly attached kinetochores by recruiting B56-PP2A phosphatase ...
The chromosomal passenger complex (CPC) localizes to centromeres in early mitosis to activate its subunit Aurora B kinase. However, it is unclear whether centromeric CPC localization contributes to CPC functions beyond Aurora B activation. Here, we show that an activated CPC that cannot localize to centromeres supports functional assembly of the outer kinetochore but is unable to correct errors in kinetochore-microtubule attachment in Xenopus egg extracts. We find that CPC has two distinct roles at centromeres: one to selectively phosphorylate Ndc80 to regulate attachment and a second, conserved kinase-independent role in the proper composition of inner kinetochore proteins. Although a fully assembled inner kinetochore is not required for outer kinetochore assembly, we find it is essential to recruit tension indicators, such as BubR1 and 3F3/2, to erroneous attachments. We conclude centromeric CPC is necessary for tension-dependent removal of erroneous attachments and for the kinetochore ...
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.
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.
Recombinant full-length human Aurora B was expressed by baculovirus in Sf9 cells using an N-terminal GST tag. Aurora B is a member of the Aurora kinase family that associates with microtubules during chromosome movement and segregation.
Hesperadin is a human Aurora B inhibitor with an IC50 of 40 nM for the prevention of the phosphorylation of substrate. Find all the information about Hesperadin for cell signaling research.
10 Feb 2016. In one of the first efforts to date to apply nanotechnology to targeted cancer therapeutics, researchers have created a nanoparticle formulation of a cancer drug that is both effective and nontoxic -- qualities harder to achieve with the free drug.. Their nanoparticle creation releases the potent but toxic targeted cancer drug directly to tumours, while sparing healthy tissue.. The findings in rodents with human tumours have helped launch clinical trials of the nanoparticle-encapsulated version of the drug, which are currently underway.. Aurora kinase inhibitors are molecularly targeted agents that disrupt cancers cell cycle.. While effective, the inhibitors have proven highly toxic to patients and have stalled in late-stage trials.. Development of several other targeted cancer drugs has been abandoned because of unacceptable toxicity.. To improve drug safety and efficacy, Susan Ashton and colleagues designed polymeric nanoparticles called Accurins to deliver an Aurora kinase B ...
ZM447439 does not prevent localization of Aurora B to centromeres. Immunofluorescence images of prometaphase DLD-1 cells stained to detect Aurora B (green), Sur
We previously reported that phosphorylation of myosin II-interacting guanine nucleotide exchange aspect (MyoGEF) by polo-like kinase 1 (Plk1) promotes the localization of MyoGEF towards the central spindle and boosts MyoGEF activity toward RhoA during mitosis. that aurora B colocalizes with MyoGEF on the central midbody and spindle during cytokinesis. Suppression of aurora B activity by an aurora B inhibitor disrupts the localization of MyoGEF towards the central spindle. Furthermore T544A mutation inhibits the localization of MyoGEF towards the cleavage furrow and reduces MyoGEF activity toward RhoA during mitosis. Used together our outcomes claim that aurora B coordinates with Plk1 to modify MyoGEF activation and localization hence adding to the legislation of cytokinesis. translated Myc-aurora B was synthesized using the TNT SP6 quick-coupled transcription/translation program (Promega Madison WI) based on the manufacturers guidelines. Coimmunoprecipitation Assays Coimmunoprecipitation assays ...
Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q(2) = 0.605, r(pred)(2) = 0.826), (q(2) = 0.52, r(pred)(2) = 0.798) and (q(2) = 0.582, r(pred)(2) = 0.971) for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond ...
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 ...
References for Abcams Recombinant Human Aurora A protein (ab86846). Please let us know if you have used this product in your publication
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 ...
Aurora B kinase, a key regulator of cell division, localizes to specific cellular locations, but the regulatory mechanisms responsible for phosphorylation of substrates located remotely from kinase enrichment sites are unclear. Here, we provide evidence that this activity at a distance depends on bo …
Its important to ask about the experience of your local Aurora lawn care companys employees before you select the company for your job. Experienced lawn care experts know which species and types of grass, shrubs and plants work best in the Aurora climate, and know how to maintain them. CVSHome.com researches local pros and partners with the ones that consistently provide the highest quality of service, and also offer competitive pricing. When you hire someone to perform lawn maintenance in Aurora, make sure that you get multiple bids, and ask for references. Even a small difference in pricing can add up over the long run, especially if you are getting frequent Aurora lawn cutting service.. ...
We present an analysis of flickering (2-10 Hz) auroras observed with a state-of-the-art multispectral imaging system, Auroral Structure and Kinetics, located in Tromso, Norway. Short (1-2 s) periods of flickering aurora have been identified in which the frequency of the brightness oscillations decreases or increases smoothly over time. To the authors knowledge this is the first detailed analysis of such chirps in flickering aurora or field-aligned bursts. We have found that the electron precipitation energy is strongly anticorrelated with the flickering frequency during all identified chirps. This result is consistent with the theory that flickering aurora is caused by the resonance interaction between electromagnetic ion cyclotron waves and precipitating electrons and that the wave parallel phase velocity is the primary factor determining the electron acceleration produced by this mechanism. Other current theories known to the authors cannot completely explain our observations.. ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
During animal cell division, the final separation of daughter cells requires ESCRT-III (endosomal sorting complex required for transport III), the core membrane scission machinery. Carlton et al. (see the Perspective by Petronczki and Uhlmann) report that ESCRT-III modulates abscission timing through one of its subunits, CHMP4C. Depletion of CHMP4C results in faster resolution of the midbody, the cytoplasmic bridge that connects the daughter cells at the end of cytokinesis. This phenotype correlates with a differential spatiotemporal distribution of CHMP4C at the midbody. As CHMP4C is essential for activating the Aurora B-mediated abscission checkpoint, consequently, depletion of CHMP4C results in the accumulation of genetic damage. Thus, the ESCRT machinery protects the cell against genetic damage by coordinating its cytokinetic activity with the abscission checkpoint.. J. G. Carlton, A. Caballe, M. Agromayor, M. Kloc, J. Martin-Serrano, ESCRT-III governs the Aurora B-mediated abscission ...
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. ...
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ZM 447439 | Aurora B inhibitor | ZM447439 | CAS [331771-20-1] | Axon 1541 | Axon Ligand™ with >99% purity available from supplier Axon Medchem, prime source of life science reagents for your research
How can we prevent mass killings like Aurora? - AP News: AURORA, Colo. (AP) - On the morning of the latest .12/12/2017 19:16:42PM EST.
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Aurora - posted in Virus, Spyware, Malware Removal: Aurora is making my computer life a misery.Here is my Hijack file... I hope you are able to help. I have run adaware and spybot, to no avail. Ive tried following the advice youve offered to other sufferers, but the file names are different in each case and I dont want to delete anything crucial. Thanks, Moggo... btw, I hope you know the geeks2go is very popular over here in England as well as in The States.Logfile of HijackThis v1.99.1Sca...
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Established in 1981, Aurora World is a global leader in plush toys and high-quality gift products, and a respected leader in the character and content industry. Aurora World offers an extensive range of branded and licensed products for children and adults ...
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Bella Aurora Labs celebrates World Science Day by announcing the opening of its new cell culture laboratory. According to the Director of Research and Deve
Browse: Home > 2016 > September > 15 > Aurora Diagnostics Welcomes Dr. Annie O. Morrision, Dermatopathologist to Our LMC Pathology Staff ...
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 ...
... 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/ ...
"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 ...
"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 ...
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 ...
"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 ...
"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 ...
Bell, G.P.; Fletcher, G.C.; Brain, R.; Thompson, B.J (2015). "Aurora kinases phosphorylate Lgl to induce mitotic spindle ... columnar pseudostratified epithelial cells must round up at mitosis in a process that involves the Aurora A and B kinases, ... Aguilar-Aragon, M.; Elbediwy, A.; Foglizzo, V.; Fletcher, G.C.; Li, V.S.W; Thompson, B.J. (2018). "Pak1 Kinase Maintains Apical ... but Cdc42 appears to act primarily via activating the kinases aPKC and Pak1 in Drosophila follicle cells. His laboratory also ...
BI811283 is a small molecule inhibitor of the aurora B kinase protein being developed by Boehringer Ingelheim for use as an ... a novel inhibitor of Aurora B kinase, on tumor senescence and apoptosis". J. Clin. Oncol. 28 (15 Suppl e13632): e13632. doi: ... Sutendra G, Michelakis ED (2013). "Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology". Frontiers in ... studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage. ...
"Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression". Blood. 114 (13): 2699-708. ...
2006). "Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma". Int. J. Cancer. 118 (2): 357-63. doi:10.1002/ ... "Entrez Gene: TTK TTK protein kinase". Hanks SK, Quinn AM (1991). "Protein kinase catalytic domain sequence database: ... Dual specificity protein kinase TTK also known as Mps1 is an enzyme that in humans is encoded by the TTK gene. GRCh38: Ensembl ... 2003). "Human MPS1 Kinase Is Required for Mitotic Arrest Induced by the Loss of CENP-E from Kinetochores". Mol. Biol. Cell. 14 ...
The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD (Jan 2005). "Sterile 20 kinase phosphorylates histone H2B at serine 10 ... SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase". Cell. 113 (4): 507-17. doi:10.1016/ ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Montgomery, K. & Mak, A.S. (1984). „In vitro phosphorylation of tropomyosin by a kinase from chicken embryo". J. Biol. Chem. ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... deBelle, I. & Mak, A.S. (1987). „Isolation and characterization of tropomyosin kinase from chicken embryo". Biochim. Biophys. ...
Aurora at Jupiter's north pole as seen in ultraviolet light by the Hubble Space Telescope. ... B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase ...
"Frequent alterations in the expression of serine/threonine kinases in human cancers". Cancer Research 66 (16): 8147-54. PMID ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ...
"BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition". J. Biol. Chem. 279 (19): 19643-8. doi:10.1074/jbc. ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... ATM/ATR are kinases activated by DNA damage. Mutation of serine residues may affect localization of BRCA1 to sites of DNA ...
1997). „Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... 1997). „Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. ENGLAND. 16 (8): 1909- ... 2003). „The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ... "Entrez Gene: CIT citron (rho-interacting, serine/threonine kinase 21)".. *^ a b c Madaule P, Furuyashiki T, Reid T, Ishizaki T ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... The complex also contains 2 regulatory enzymes, a kinase and a phosphorylase. The BCKDHA gene encodes the alpha subunit of E1, ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3». ... full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2». Cancer Res. 69 (3 ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... O'Brien, K A; Lemke S J, Cocke K S, Rao R N, Beckmann R P (1999). «Casein kinase 2 binds to and phosphorylates BRCA1». Biochem ...
"Protein kinase C and lipid signaling for sustained cellular responses" (ABSTRACT). FASEB J. 9 (7): 484-96. PMID 7737456 ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... "The extended protein kinase C superfamily". Biochem. J. 332 ( Pt 2): 281-92. PMC 1219479. PMID 9601053 ...
Soderling TR (1999). „The Ca-calmodulin-dependent protein kinase cascade". Trends in Biochemical Sciences. 24 (6): 232-6. PMID ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... Lisman, J. E. (1985) A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase. ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... kinase activity. • protein binding. • ATP binding. • protein serine/threonine kinase activity. • protein kinase activity. ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein kinase activity. • protein serine/threonine kinase activity. • protein binding. • ATP binding. • magnesium ion binding ... Microtubule-associated serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MAST1 gene.[5] ...
Dhillon AS, Kolch W (2002). "Untying the regulation of the Raf-1 kinase". Arch. Biochem. Biophys. 404 (1): 3-9. PMID 12127063. ... Aurora kinaza (Aurora A kinaza, Aurora B kinaza). Fas-aktivirana serin/treoninska kinaza (EC 2.7.11.8) ... Li P, Wood K, Mamon H, Haser W, Roberts T (February 1991). "Raf-1: a kinase currently without a cause but not lacking in ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... protein kinase binding. • protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ... kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ...
Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical ... "Casein Kinase II (CK2) as a Therapeutic Target for Hematological Malignancies". Current Pharmaceutical Design. 23 (1): 95-107. ... kinase (PI3K)/AKT axis, Hedgehog signaling pathway, nuclear factor-kappaB and Activating Transcription Factor 2 have also been ... is a potent TGF-β type I receptor kinase inhibitor that was demonstrated to reduce the size, the growth rate of tumors, and the ...
For example, phosphorylation of Serine 194 on RalA by the kinase Aurora A results in the relocation of RalA to the inner ... whereas phosphorylation of Serine 198 on RalB by the kinase PKC results in the relocation of RalB to other internal membranes ...
... it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting ... Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, Boehlecke B, Chesson AL Jr, Friedman L, Maganti R, Owens J, ... Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its ... calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5.. Figure 2 ...
December 2012). "Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence after chemotherapy in patient- ... Utilizing PDX triple negative breast cancer models, scientists found that aurora kinase inhibitors slows tumor growth rate and ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for ... This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide ...
Aurora at Jupiter's north pole as seen in ultraviolet light by the Hubble Space Telescope. ... B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... protein serine/threonine kinase activity. • ATP binding. • kinase activity. • protein binding. Cellular component. • cell ... Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.[5][6][7] ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... kinase activity. • protein binding. • RNA polymerase II carboxy-terminal domain kinase activity. • ATP binding. • protein ... Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.[5][6] ...
... full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Research. 69 ... kinase binding. • RNA binding. • protein heterodimerization activity. • ubiquitin-protein transferase activity. • protein ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... A major target of Akt kinases is glycogen synthase kinase-3. EC 2.7.1.37 Pelle. is a serine/threonine kinase that can ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... A serine/threonine protein kinase (EC 2.7.11.1) is a kinase enzyme that phosphorylates the OH group of serine or threonine ( ...
Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein kinase activity. • cAMP-dependent protein kinase activity. • ADP binding. • AMP-activated protein kinase activity. • ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... cAMP-dependent protein kinase regulator activity. • protein kinase binding. • ATP binding. • adenyl ribonucleotide binding. ...
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 human genome contains three members the Aurora kinase family: Aurora A kinase, Aurora B kinase and Aurora C kinase. The ... Aurora A and Aurora B kinases play important roles in mitosis. The Aurora A kinase is associated with centrosome maturation and ... Aurora A phosphorylation directs the cytoplasmic polyadenylation translation of mRNAs, like the MAP kinase kinase kinase ... contain orthologues only to Aurora A and Aurora B. In all studied species, the three Aurora mitotic kinases localize to the ...
Aurora kinase Aurora A kinase Aurora C kinase INCENP Spindle assembly checkpoint GRCh38: Ensembl release 89: ENSG00000178999 - ... Phosphorylation of CENP-A at serine 7 by Aurora A kinase recruits Aurora B to the centromere. Aurora B, itself, can also ... The Aurora kinases associate with microtubules during chromosome movement and segregation. Aurora kinase B localizes to ... Aurora B kinase has been shown to interact with: BARD1, BIRC5, and CDCA8 TACC1. FBXL2. Abnormally elevated levels of Aurora B ...
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-A kinase complexed with AMPPNP. Kukimoto-Niino, M., Murayama, K., Shirouzu, M., Yokoyama, S.. To be published. ... Serine/threonine-protein kinase 6. A. 285. Homo sapiens. Mutation(s): 3 Gene Names: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, ...
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, ...
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? ...
... 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) ...
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.PROSITE-ProRule annotation. Manual ...
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-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Sasai, ... Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. Yang, H., Burke, T., Dempsey, J., Diaz, ... Human Aurora/Ipl1-related kinase 2 (Aurora-B) is a key regulator of mitosis [19]. ... Inactivation of aurora A activates checkpoint kinase BubR1 in an aurora B-dependent manner [27]. ...
Aurora Kinase B (Aurora 1 or Aurora And IPL1 Like Midbody Associated Protein 1 or Serine/Threonine Protein Kinase 12 or Serine/ ... Kinase B - Pipeline Review, H2 2018 drug pipelines has been added to ResearchAndMarkets.coms offering. ... Aurora Kinase B (Aurora 1 or Aurora And IPL1 Like Midbody Associated Protein 1 or Serine/Threonine Protein Kinase 12 or Serine/ ... Threonine Protein Kinase 5 or Serine/Threonine Protein Kinase Aurora B or STK1 or AURKB or EC 2.7.11.1) pipeline Target ...
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 ...
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... 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 ...
  • Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. (nih.gov)
  • 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 is a selective small-molecule Aurora A kinase inhibitor that has entered Phase I clinical trials for advanced solid tumors. (pnas.org)
  • 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)
  • In this report, we describe MLN8054, an orally active small-molecule inhibitor of Aurora A kinase that has entered clinical development. (pnas.org)
  • MLN8054, a Potent and Selective Inhibitor of Aurora A Kinase Activity. (pnas.org)
  • MLN8054 was the first orally administered Aurora A–selective inhibitor to be tested in human clinical trials for the treatment of colorectal cancer. (biovision.com)
  • MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. (selleckchem.com)
  • 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)
  • The effect of the clinical Aurora-kinase inhibitor VX680 on proliferation of 20 human-myeloma-cell-lines and survival of 5 primary myeloma-cell-samples was tested. (archives-ouvertes.fr)
  • 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)
  • Cambridge, Mass.-based Millennium will face more direct competition from EntreMed Inc., of Rockville, Md., with its Aurora A/angiogenic kinase inhibitor ENMD-2076. (bioworld.com)
  • 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)
  • 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)
  • 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)
  • Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. (sigmaaldrich.com)
  • This phase I study (ClinicalTrials.gov ID: NCT00424632) evaluated the safe dose, pharmacokinetics, and pharmacodynamics of the aurora kinase A and B inhibitor, PF-03814735. (sigmaaldrich.com)
  • We have studied the preclinical pharmacology of BI 847325, an ATP-competitive dual inhibitor of MEK and Aurora kinases. (aacrjournals.org)
  • Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib. (auth.gr)
  • To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. (auth.gr)
  • Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. (auth.gr)
  • The discovery that activated forms of Aurora A can have different dynamic properties raises the possibility that inhibitor molecules could be designed to exploit these differences and block specific activities of Aurora A in cancer cells. (elifesciences.org)
  • Importantly, concurrent inhibition of NIK or c-Abl disrupts Aurora inhibitor-induced feedback activation of STAT3 and sensitizes myeloma cells to Aurora inhibitors, implicating a combined inhibition of Aurora and NIK or c-Abl kinases as potential therapies for multiple myeloma. (haematologica.org)
  • 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)
  • 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 Aurora Kinase Inhibitor II, also referenced under CAS 331770-21-9, controls the biological activity of Aurora Kinase. (merckmillipore.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)
  • 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 Aurora Kinase/Cdk Inhibitor, also referenced under CAS 443797-96-4, controls the biological activity of Aurora Kinase/Cdk. (merckmillipore.com)
  • A cell-permeable triazolylsulfonamido compound that acts a reversible, ATP-competitive kinase inhibitor with selectivities towards Aurora kinases (IC 50 = 11 and 15 nM for Aurora-A, Aurora-B, respectively) and Cdk's (IC 50 = 9, 4, and 3 nM for Cdk1/B, Cdk2/A, and Cdk2/E, respectively). (merckmillipore.com)
  • The Aurora Kinase Inhibitor III, also referenced under CAS 879127-16-9, controls the biological activity of Aurora Kinase. (emdmillipore.com)
  • 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)
  • We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. (inserm.fr)
  • SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery tool. (semanticscholar.org)
  • We characterize the screen using a focused tool compound kinase inhibitor library. (gla.ac.uk)
  • 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)
  • 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)
  • Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors. (escholarship.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)
  • 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)
  • It has recently been demonstrated that Coenzyme A (CoA) is a highly selective ATP-competitive inhibitor of Aurora A kinase. (ucl.ac.uk)
  • The first, conserved the pantothenamide tail and focused on replacing the adenosine moiety of CoA with a heteroaromatic head group based around VX680 - a known inhibitor of the Aurora kinases. (ucl.ac.uk)
  • 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)
  • Phosphorylation of CENP-A at serine 7 by Aurora A kinase recruits Aurora B to the centromere. (wikipedia.org)
  • Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. (uniprot.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 2.7.11.1) 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 serine/threonine kinases that function as key regulators of mitosis and are frequently overexpressed in human cancers. (eur.nl)
  • 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 2.7.11.1) 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 2.7.11.1) 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 2.7.11.1) - Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that contributes to the regulation of cell cycle progression. (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 2.7.11.1) 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 2.7.11.1) - 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 2.7.11.1) 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)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (rush.edu)
  • 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)
  • Localization of Aurora B to the centromere during prometaphase and metaphase requires phosphorylation of the mammalian kinetochore-specific histone-H3 variant centromere protein A (CENP-A). CENP-A associates with the centromere and is necessary for assembly of the kinetochore. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Many eukaryotic protein kinases are activated by phosphorylation on a specific conserved residue in the regulatory activation loop, a post-translational modification thought to stabilize the active DFG-In state of the catalytic domain. (elifesciences.org)
  • Here we use a battery of spectroscopic methods that track different catalytic elements of the kinase domain to show that the ~100 fold activation of the mitotic kinase Aurora A (AurA) by phosphorylation occurs without a population shift from the DFG-Out to the DFG-In state, and that the activation loop of the activated kinase remains highly dynamic. (elifesciences.org)
  • The enzymes that catalyze this process, called protein kinases, are themselves controlled by the phosphorylation of a flexible region called the activation loop. (elifesciences.org)
  • For many years it had been thought that the purpose of activation loop phosphorylation was to clamp the otherwise flexible activation loop in an active state that allows molecules that need to be phosphorylated to bind to the kinase. (elifesciences.org)
  • In the absence of phosphorylation on the activation loop, kinase activity is usually restrained by rearrangements of the activation loop and DFG motif into specific autoinhibited conformations. (elifesciences.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)
  • Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. (inserm.fr)
  • 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)
  • 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)
  • Chromosomal segregation during mitosis as well as meiosis is regulated by kinases and phosphatases. (wikipedia.org)
  • Expression of Aurora B reaches a maximum at the G2-M transition, whereas Aurora B protein is most active during mitosis. (wikipedia.org)
  • This analysis showed that the association of Aurora B with centromeres is dynamic (Aurora B at the centromere is constantly exchanging with a pool of cytoplasmic Aurora B). The analysis of tagged Aurora B also suggested that it associates with spindle microtubules during anaphase of mitosis and this association significantly limits its mobility. (wikipedia.org)
  • In topoisomerase II-depleted cells, Aurora B and INCENP do not transfer to the central spindle in late 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)
  • 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)
  • Mitosis begins in mammalian cells when a protein accumulates between cell divisions and interacts with a second protein to initiate a cascade of kinase activation. (sciencemag.org)
  • 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)
  • BACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. (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)
  • 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)
  • 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)
  • We performed chemical and genetic vulnerability screens in RB1-isogenic lung cancer pair and herein report that aurora kinase A (AURKA) inhibition is synthetic lethal in RB1-deficient lung cancer. (nature.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)
  • Numerous kinetochore targets of Aurora kinases have been determined in organisms ranging from yeast to man. (wikipedia.org)
  • 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)
  • The findings reveal an important functional interaction between NIK, Abl and Aurora kinases, and identify the NIK, c-Abl and PIM survival kinases as potential pharmacological targets for improving the efficacy of Aurora inhibitors in myeloma. (haematologica.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)
  • We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. (inserm.fr)
  • 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)
  • 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)
  • Aurora B has been shown to bind to end-binding protein 1 (EB1), a protein that regulates microtubule dynamics. (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)
  • Aurora A regulates several important steps in cell division, and plays important roles in several kinds of cancer. (elifesciences.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)
  • 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)
  • show that the static model is incorrect in a protein kinase called Aurora A. In this enzyme, the phosphorylated activation loop continues to switch back and forth between active and inactive states. (elifesciences.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)
  • 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)
  • Aurora A localizes next to the centrosome late in the G1 phase and early in the S phase. (wikipedia.org)
  • γ-tubulins, the base structure from which centrosomal microtubules polymerize, are also recruited by Aurora A. Without Aurora A the centrosome does not accumulate the quantity of γ-tubulin that normal centrosomes recruit prior to entering anaphase. (wikipedia.org)
  • Aurora A is important in centrosome function and duplication, mitotic entry and bipolar spindle assembly. (biovision.com)
  • 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)
  • Aurora Kinase 2 overexpression leads to centrosome amplification, chromosome instability and transformation in mammalian cells. (leicabiosystems.com)
  • 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)
  • Our data further show that estrogens, interacting with the estrogen receptor α, elicit persistent Aurora A kinase over expression that may affect abnormal centrosome duplication, and together with the loss of p53wt activity by the over expression of MDM2 lead to estrogen-induced oncogenesis. (ku.edu)
  • Consistent with its role in spindle formation, aurora A kinase associates with the centrosome and microtubules. (biologists.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)
  • 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)
  • These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. (embopress.org)
  • 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)
  • Aurora B complexes with three other proteins, Survivin, Borealin and INCENP. (wikipedia.org)
  • 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)
  • RESULTS: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. (inserm.fr)
  • Synthetic peptide near the C-terminus of human Aurora kinase A, B, and C proteins. (roche.com)
  • Inhibitors of aurora kinases were shown to induce apoptosis in vitro and in vivo. (nih.gov)
  • 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)
  • 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)
  • 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)
  • 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)
  • Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT. (inserm.fr)
  • 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)
  • 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)
  • Intriguingly, EB1 overexpression enhances Aurora B kinase activity, at least in part because EB1 blocks the dephosphorylation/inactivation of Aurora B by protein phosphatase 2A. (wikipedia.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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Indirect immunofluorescence showed that Aurora B and EB1 colocalize during anaphase on the central spindle and in the midbody during cytokinesis. (wikipedia.org)
  • 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)
  • 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)
  • 4 2 Among these, mutations in the genes encoding NF-κB-inducing kinase (NIK) or its negative regulators TRAF2, TRAF3, cIAP1, and cIAP2 lead to increased stability of NIK and subsequent aberrant activation of the non-canonical and canonical NF-κB pathways. (haematologica.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)
  • 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)
  • The use of several small molecule aurora kinase inhibitors as potential anticancer therapeutic is being investigated. (eur.nl)
  • Millennium said it believes that inhibition of Aurora kinase causes anomalies to occur during cell division, leading to apoptosis. (bioworld.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)
  • 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)
  • Interestingly, danusertib also inhibits several receptor tyrosine kinases such as Abl, Ret, FGFR-1 and TrkA. (eur.nl)
  • These tyrosine kinases are involved in the pathogenesis of a variety of malignancies and the observed multi-target inhibition may increase the antitumor activity resulting in extending the indication. (eur.nl)
  • Completing the structural family portrait of the human EphB tyrosine kinase domains. (semanticscholar.org)
  • 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)
  • 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)
  • Danusertib (formerly PHA-739358) is a small ATP competitive molecule that inhibits aurora A, B and C kinases. (eur.nl)
  • 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)
  • 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)
  • Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237. (semanticscholar.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)
  • 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)
  • In 1998, Aurora kinase B was identified in humans by a polymerase chain reaction screen for kinases that are overexpressed in 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)
  • 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)
  • 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)
  • 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)
  • CONCLUSIONS: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment. (inserm.fr)
  • 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)
  • 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)
  • Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. (wikipedia.org)
  • Specifically, Aurora B localizes to the chromosomes in prophase, the centromere in prometaphase and metaphase, and the central mitotic spindle in anaphase. (wikipedia.org)
  • Studies in several organisms indicate that Aurora B oversees chromosome biorientation by ensuring that appropriate connections are made between spindle microtubules and kinetochores. (wikipedia.org)
  • Inhibition of Aurora B function by RNA interference or microinjection of blocking antibodies impairs the alignment of chromosomes at the equator of the mitotic spindle. (wikipedia.org)
  • Aurora B inhibition may lead to an increase in the number of syntelic attachments (sister chromatid pairs in which both sister kinetochores are attached to microtubules radiating from the same spindle pole). (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)
  • 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)
  • 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)
  • Intriguingly, expression of a dominant-negative and catalytically inactive form of Aurora B disrupted microtuble attachment to the kinetochore and prevented the association of dynein and centromere protein E (CENP-E) with kinetochores. (wikipedia.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)
  • 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)
  • Additionally, topoisomerase II has been implicated in the regulation of Aurora B localization and enzymatic activity. (wikipedia.org)
  • Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. (asm.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)
  • 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)
  • 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)
  • A more detailed analysis of Aurora B localization has been carried out in mammalian cells by tagging Aurora B with green fluorescent protein. (wikipedia.org)
  • In addition, disruption of Aurora A protein in tumor cells delays mitotic entry and progression, resulting in the accumulation of cells in the G 2 /M cell cycle phase ( 9 - 13 ). (pnas.org)
  • Network analysis shows how the kinase Plk1 supports the mitotic activity of Aurora A. (sciencemag.org)
  • We show that this recruitment depends on both activity of Plk1, a kinetochore-localized kinase, and activity of Aurora B itself. (elsevier.com)
  • Danusertib was one of the first aurora kinase inhibitors to enter the clinic and has been studied in Phase I and II trials. (eur.nl)
  • [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)
  • In humans, these enzymes share 75% sequence homology in their kinase domains ( 1 , 2 ). (pnas.org)
  • Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 was demonstrated in enzymatic and cellular assays. (aacrjournals.org)
  • 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)
  • 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)
  • Mechanistically, we demonstrate that Aurora inhibition promotes NIK protein stabilization via downregulation of its negative regulator TRAF2. (haematologica.org)
  • 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)
  • 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)
  • 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)
  • Members of the aurora kinase family regulate a range of mitotic processes. (biologists.org)
  • Therefore, without proper expression of Aurora A, the cell's centrosomes are never able to separate. (wikipedia.org)
  • For example, deletion of Aurora A in C. elegans results in an initial separation of the cell's centrosomes followed by an immediate collapse of the asters. (wikipedia.org)
  • 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. (wikipedia.org)
  • Although there is evidence to suggest that Aurora C might be a chromosomal passenger protein, the cellular function of it is less clear. (wikipedia.org)
  • Aurora B is a chromosomal passenger protein. (wikipedia.org)
  • The catalytic activity of protein kinases is regulated by finely-tuned allosteric mechanisms that reversibly switch the kinase domain between active and inactive conformational states ( Huse and Kuriyan, 2002 ). (elifesciences.org)
  • 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)
  • Increased Aurora A expression may lead to increased kinase activity, which is thought to contribute to tumor initiation and progression ( 20 ). (pnas.org)
  • 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)
  • 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)