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.
76 Jobs. 13 talking about this. Find Aurora University reviews, tuition costs and how many students are enrolled at Aurora University in Illinois. View All num of num Close (Esc) Aurora University. Companies. Program Details. $38,798. Founded as a seminary in 1893, Aurora University has expanded its mission to build an inclusive community based on four values: integrity, citizenship, continuous learning and excellence. The Bachelor of Science in Nursing training program at Aurora University incorporates a solid foundation in the sciences with professional training and also significant clinical experiences. Aurora University . Aurora University - Dunham School of Business , Student reviews, Accreditation, Tuition fees and Scholarships, Price and Cost, Rankings, Application, Admission requirements, Curriculum, Class profile, Salary and Jobs, GMAT,IELTS and TOEFL scores Note: there are allegations of misconduct involving Aurora Police Brass and corrupt Aurora Mayor Tom Weisner to cover up … ...
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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.. ...
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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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Welcome to the official website of City of Aurora. Aurora is Colorados third largest city with a diverse population of more than 381,000. From agricultural outpost to military bastion, Aurora established its foundation as a driving force in the west.
Welcome to the official website of City of Aurora. Aurora is Colorados third largest city with a diverse population of more than 381,000. From agricultural outpost to military bastion, Aurora established its foundation as a driving force in the west.
The Cotton Seed Creative Exchange, 8 N. Broadway, features nearly a dozen artisans who offer clever, handcrafted signs, unique coasters, fun home decor, and vintage albums. Aurora Downtown merch such as hoodies, candles, and t-shirts are also available at the shop. Down the street, Patron Boots is filled with leather boots and menswear. There are more than a dozen shops and salons to visit along Broadway. ...
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.
"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 ...
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. ...
... 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) ...
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- ...
... 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 ...
... 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 ...
"P21-activated kinase 7 mediates cisplatin-resistance of esophageal squamous carcinoma cells with Aurora-A overexpression". PLOS ... Selectivity of PAK5 signaling was recognized by its ability to stimulate the JNK kinase but not p38 or ERK kinases. The PAK5 ... PAK5 expression is positively regulated by Aurora-A and both PAK5 and Aurora-A are co-upregulated in esophageal squamous ... Serine/threonine-protein kinase PAK 5 is an enzyme that in humans is encoded by the PAK5 gene. The PAK5 enzyme is one of three ...
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: ... studies with introducing thymidine kinase in gliomas, making them susceptible to aciclovir, are in their experimental stage. ...
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 ...
Zeitlin SG, Shelby RD, Sullivan KF (December 2001). "CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role ... December 2003). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and ...
Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP ... The ARK binding region has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has ... Leverson JD, Huang HK, Forsburg SL, Hunter T (April 2002). "The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts ... and aurora-B kinase during male mouse meiosis". J. Cell Sci. 116 (Pt 6): 961-74. doi:10.1242/jcs.00330. PMID 12584241. ...
... has been shown to interact with: Aurora A kinase, Aurora B kinase, BARD1, CKAP5, LSM7, SNRPG, and TDRD7. GRCm38: Ensembl ... full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Res. 69 (3 ... Delaval B, Ferrand A, Conte N, Larroque C, Hernandez-Verdun D, Prigent C, Birnbaum D (2004). "Aurora B -TACC1 protein complex ... "TACC1-chTOG-Aurora A protein complex in breast cancer". Oncogene. 22 (50): 8102-16. doi:10.1038/sj.onc.1206972. PMID 14603251. ...
"Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model". ... "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation". The ... "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation". The ... and drug sensitivity are preferentially regulated by anti-HER2 antibody through phosphatidylinositol 3-kinase-AKT signaling". ...
2002). "Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell ... 2002). "The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not ... "Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation". J. Biol. Chem ...
2004). "Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model". ... "Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1". Chromosoma. 113 (1): 1-15. ...
2000). "Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and ...
2000). "Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and ... Goto H, Yasui Y, Nigg EA, Inagaki M (2002). "Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic ... "Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase". Nucleic Acids Res. 31 (3): 878-85. ...
... role in the spindle checkpoint during mitosis thus interacts with spindle assembly proteins Aurora A kinase and Aurora B kinase ... Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. Two checkpoint kinase subtypes have been ... WEE1 kinase and PLK1 are also targeted by Chk1 to induce cell cycle arrest. Phosphorylation of WEE1 kinase inhibits cdk1 which ... Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by ...
... like Aurora B kinase, Survivin and INCENP. Direct phosphorylation of INCENP by Bub1 has been observed. RNAi mediated depletion ... domain and a C-terminal kinase domain (residues 784-1085), adopting a canonical kinase fold with two lobes. The ATP binding and ... The protein kinase Bub1 possesses versatile and distinct functions during the cell cycle, mainly in the SAC and chromosome ... Jang YJ, Ji JH, Choi YC, Ryu CJ, Ko SY (Jan 2007). "Regulation of Polo-like kinase 1 by DNA damage in mitosis. Inhibition of ...
... and Aurora A kinase". J. Biol. Chem. 285 (29): 22196-201. doi:10.1074/jbc.M109.069344. PMC 2903397. PMID 20460379. Zhan Q, ... 1999). "Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45". Oncogene. ... Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (September 2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors ... 2000). "The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression". J. Biol. Chem. 275 (22): ...
Phosphorylation of H3 at serine 10 (phospho-H3S10) The mitotic kinase aurora B phosphorylates histone H3 at serine 10, ... Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD (January 2005). "Sterile 20 kinase phosphorylates histone H2B at serine ... SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... May 2003). "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase". Cell. 113 (4): 507-17. ...
This led to genetic studies that allowed him to discover and name the Polo and Aurora protein kinases, required for the ... In Cambridge he discovered the second main Aurora B kinase required for cells to progress through metaphase and used genetic ... Over the past decade he has uncovered the major steps of centriole duplication by demonstrating that Polo-like-kinase 4 (Plk4) ... Remarkably, the localisation and function of Polo kinase at the centrosome, the kinetochore and the central spindle in ...
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 ... and with Sec5 to activate the innate immune response via the Tank-binding kinase 1 (TBK1). Ral proteins have been associated ... "RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival". Cell ...
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 ...
... may refer to: Aurora A kinase, an enzyme Myosin-heavy-chain kinase, an enzyme This disambiguation page lists articles ...
Aurora A and B kinases (STK6 and STK12), E2F5, and CDK8, among others. Subsequent experiments confirmed the direct effects of ... Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM, Minn AJ, Rosner MR (2009). "Raf kinase inhibitory protein ... and Stabilization of Wee1 Kinase in Primary Fibroblasts". J Biol Chem. 284 (11): 6605-9. doi:10.1074/jbc.C900002200. PMC ...
Aurora kinase inhibitors are a putative drug class for treating cancer. The Aurora kinase enzymes could be potential targets ... There are three mammalian aurora kinase genes, encoding aurora A, B and C. Intense investigation has focused on aurora A and B ... Aurora-B (Serine/threonine-protein kinase 12, AIK2, AIM1, ARK2, STK12) Aurora-C (Serine/threonine-protein kinase 13, AIE2, AIK3 ... Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have ...
Gruneberg U, Neef R, Honda R, Nigg EA, Barr FA (2004). "Relocation of Aurora B from centromeres to the central spindle at the ... "Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis". J. Cell Biol. 162 (5): ...
The CHEK1 (checkpoint kinase 1) gene, located at chromosome position 11q24.2, is responsible for encoding the protein kinase ... Porrello ER, Johnson BA, Aurora AB, Simpson E, Nam YJ, Matkovich SJ, et al. (2011). "MiR-15 family regulates postnatal mitotic ...
Wirtz-Peitz F, Nishimura T, Knoblich JA (October 2008). "Linking cell cycle to asymmetric division: Aurora-A phosphorylates the ... 1995). "A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution". ... atypical protein kinase C). In the sensory organ precursor (SOP) cell, the PAR proteins localize to the posterior pole of the ...
Many protein kinases can regulate activity of the ATG5 protein. Phosphorylation by various kinases are required in order to ... nucleus and interacting with survivin to disturb chromosome segregation by antagonistically competing with the ligand Aurora B ... protein will interact with MAPK/ERK kinase kinase 4 (MEKK4) to form the Gadd45ß-MEKK4 signaling complex. This complex then ... DNA damage induces the p300 acetylase to acetylate p73 with the assistance of c-ABL tyrosine kinase. p73 translocates to the ...
2004). "Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2 ... 2007). "Phospho-regulation of HsCdc14A By Polo-like kinase 1 is essential for mitotic progression". J. Biol. Chem. 282 (37): ...
Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG (November 1997). "The cyclin-dependent kinase-activating kinase (CAK) assembly ... Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO (1994). "Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA ... Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG (1997). "The cyclin-dependent kinase-activating kinase (CAK) assembly factor, ... Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (1993). "The solution structure of the Oct-1 POU-specific domain ...
Goto H, Yasui Y, Nigg EA, Inagaki M (January 2002). "Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic ... Zhong S, Zhang Y, Jansen C, Goto H, Inagaki M, Dong Z (April 2001). "MAP kinases mediate UVB-induced phosphorylation of histone ...
... 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 ... σ-2 Receptors modulate DAT and the release of dopamine via protein kinase C (PKC) and Ca2+-calmodulin systems [14]. σ-1 ...
review the different activation mechanisms of the Aurora A kinase during mitotic entry and progression. ... Aurora B kinase, Polo-like kinase 1 (Plk1), and Cyclin-dependent kinase 1 (Cdk1)/Cyclin A/B complexes. Their precise and ... Aurora A kinase activation: Different means to different ends Nicolas Tavernier, Nicolas Tavernier ... Aurora A is a serine/threonine kinase essential for mitotic entry and spindle assembly. Recent molecular studies have revealed ...
Aurora kinase inhibitors are a putative drug class for treating cancer. The Aurora kinase enzymes could be potential targets ... There are three mammalian aurora kinase genes, encoding aurora A, B and C. Intense investigation has focused on aurora A and B ... Aurora-B (Serine/threonine-protein kinase 12, AIK2, AIM1, ARK2, STK12) Aurora-C (Serine/threonine-protein kinase 13, AIE2, AIK3 ... Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have ...
Evaluation of transcripts linked to signaling pathways recommended a job for MAP kinases, GTPases, and LKBP1/AMP kinases linked ... The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinaseMAP3K7/TAK1 ... The full total leads to Shape ?Shape88 showed that at 20 nM substance 3f was dynamic against a genuine amount of kinases ... and WNT-1. This protein interacts and thus activatesTAK1 kinase. It has been shown that the C-terminal portion of this protein ...
The Aurora Kinases in Cancer therapy. Tag: EYA1. Arachidonic acid is certainly metabolized to 4 regioisomeric ...
"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 ...
Supplementary Materialscells-08-01514-s001. in normal T cells. Oxidative stress and cell death are limited in memory T cells and we found that PDI inhibition promoted memory traits and reshaped T cell metabolism. Using adoptive transfer of tumor antigen-specific CD8 T cells, we demonstrate that T cells activated and expanded in the presence of E64FC26 control tumor growth better than vehicle-matched controls. Our data indicate that PDI inhibitors are a new class of drug that may dually inhibit tumor cell growth and improve T cell tumor control. value 0.05 and fold-change boundary of 2.0 considered to determine significant differences in gene expression. Tumor growth is analyzed by linear regression of growth curves of vehicle versus drug-treated T cells. Survival to 30 days or tumor size of 200 mm2 with Log-rank test for survival proportions of mice treated with vehicle versus E64FC26-treated T cells was used for analysis. Data are presented as standard error of the mean, SEM. Unless otherwise ...
This study analyzes the effect of highly active antiretroviral therapy (HAART), and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies diversity in patients coinfected with the human immunodeficiency virus (HIV) and HCV. group C experienced significantly higher CD4+- and CD8+-cell counts, a tendency toward a higher HCV weight, and improved variety of HCV clones considerably, entropy, genetic length, and proportion of nonsynonymous substitutions per nonsynonymous site to associated substitutions per associated site (than those contaminated with genotype 1. These total outcomes claim that there is absolutely no instant aftereffect of HAART on HCV but that, with extended HAART, immune system restoration outcomes within an upsurge in HCV quasispecies and insert diversity. As a complete consequence of common settings of transmitting, the entire prevalence of hepatitis C pathogen (HCV) infections among individual immunodeficiency pathogen (HIV)-infected people is certainly ...
BRAF and the MAP Kinase Pathway BRAF is definitely a protein kinase that activates the MAP kinase/ERK-signaling pathway.7 BRAF ... such as for example mitogen-activated proteins kinase (MAPK), proteins kinase C (PKC), proteins kinase A (PKA), cdc2/cyclin v- ... Focusing on the BRAF and the MAP Kinase Pathway Investigators have very long known the triggered MAP-kinase pathway, which ... ERK1 and 2 will be the most studied MAP kinases probably. * Post author By technumber ...
As an innovative chemical database for commercial sourcing,acesobio Technology mainly offers building blocks and screening compounds used in drug discovery and pre-clinical development, including inventory trading and synthetic services. acesobioTechnolog
Inhibition of Aurora Kinase potentiates the anti-tumour activity of Paclitaxel in Urothelial Cell Carcinoma ... Inhibition of Aurora Kinase potentiates the anti-tumour activity of Paclitaxel in Urothelial Cell Carcinoma ...
... casein kinase 1 (CKI)a, and adenomatous polyposis coli (APC). -catenin interacts with this complicated and is after that ...
Gastric cancer (GC) is definitely the 4th and 5th many common cancer in men and women, respectively. cells. Silencing of endogenous filamin C improved tumor cell migration and intrusion, whereas ectopic appearance of filamin C got rival results. Silencing of filamin C improved the appearance of matrix metallopeptidase 2 and improved the metastasis of prostate tumor in a zebrafish model. Large filamin C connected with better diagnosis of prostate tumor, leukemia and breasts tumor individuals. These results set up a practical part of filamin C in human being malignancies and these data will become important for additional research of its systems. in GC or prostate tumor cell lines improved cell migration and intrusion, whereas overexpression inhibited the migration and intrusion of malignancies cells. Our outcomes recommend that filamin C can be a growth suppressor included in the advancement of GC and prostate tumor. Outcomes In depth proteomic evaluation of GC cell appearance by label-free LC-MS ...
Aurora B kinase controls the targeting of the Astrin-SKAP complex to bioriented kinetochores ... Localization of the spindle and kinetochore proteins Astrin, SKAP, and LC8 is antagonized by Aurora B so that they target… ...
AurKa Pharma is a company established by TVM Capital Life Science to develop oncology compound AK-01, an Aurora kinase A ...
... deactivates various receptor tyrosine kinases; alters cell cycle transcription/translation; modulates mitochondrial respiration ... Metformin has AMP-kinase (AMPK) dependent and independent mechanisms of action, most notably affecting the liver and skeletal ... Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] ... Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory ...
Abstract B24: Differential sensitivity to Aurora kinase inhibition in RIT1- and KRAS-mutant lung adenocarcinoma Clinical Cancer ... Abstract 2726: Functional multiomic profiling identifies Aurora kinase inhibition as a therapeutic strategy inRIT1-mutant lung ... Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ... P2.03b-042 MET exon 14 Mutations Encode a Hyperactive Kinase and Therapeutic Target in Lung Adenocarcinoma Journal of Thoracic ...
Calbiochem TAM Receptor Kinase Inhibitor, LDC1267, is a cell-permeable, tight-binding type II TAM kinase inhibitor (IC₅₀ = 8 ... Also displays inhibitory activity against Met, Aurora B, Lck, and Src, but only at relatively higher concentration (IC50 = 35, ... TAM Receptor Kinase Inhibitor, LDC1267 - CAS 1361030-48-9 - Calbiochem. 533850 Sigma-AldrichTAM Receptor Kinase Inhibitor, ... TAM Receptor Kinase Inhibitor, LDC1267, is a cell-permeable, tight-binding "type II" TAM kinase inhibitor (IC₅₀ = 8, 29 & 5 nM ...
aurora kinase A. 0.012. Yeast Zebrafish Mouse Worm Ccl4. chemokine (C-C motif) ligand 4. 0.012. ... v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma). 0.015. ... mitogen-activated protein kinase kinase kinase kinase 4. 0.015. Grin2b. glutamate receptor, ionotropic, N-methyl D-aspartate 2B ...
Description : protein kinase (AURORA). protein kinase (AUR). protein kinase (Aurora). Gene families : OG0078426 (Archaeplastida ...
Aurora A kinase 318. 118. 0.01. -0.79. 0.37. 0.58. Cancer. 1,053,491. Disease. Disease. Disabilities. 28,757. 440. 0.00. -0.99 ...
AURKA; AIK; ARK1; AURA; BTAK; PPP1R47; STK15; STK6; STK7; aurora kinase A ...
Aurora Pathway. The three Aurora mitotic kinases localize to the centrosome during different phases of mitosis.. Search. Main ... Posted in Aurora Pathway , Leave a reply The two left and suitable phage ends in the host/phage junction i. Posted on May 29, ... Posted in Aurora Pathway , Leave a reply The qRT PCR examination was made use of to evaluate the dynamic e. Posted on May 28, ... Posted in Aurora Pathway , Leave a reply As to the microarray ana lysis, p values have been adjusted from. Posted on May 27, ...
Aurora Pathway. The three Aurora mitotic kinases localize to the centrosome during different phases of mitosis.. Search. Main ... Posted in Aurora Pathway , Leave a reply 05) (Fig 5b) Except for the L paracasei F19 strain, biofilm fo. Posted on February 27 ... Posted in Aurora Pathway , Leave a reply Painless and gentle dental treatment is a high. priority t. Posted on February 25, ... Posted in Aurora Pathway , Leave a reply Until data are available, this preparation is not advised for thi. Posted on February ...
The MOA Work Group established four subteams to develop tubulin binding, topoisomerase II inhibition, aurora kinase inhibition ... thymidine-kinase-mammalian-cell-mutagenicity-assays-for-assessment-of-nanomaterials [to_ping] => [pinged] => [post_modified ...
The MOA Work Group established four subteams to develop tubulin binding, topoisomerase II inhibition, aurora kinase inhibition ...
aurora kinase A [Source:HGNC Symbol;.... AZI2. 64343. AZI2. 5-azacytidine induced 2 [Source:HGNC.... ...
Aurora Kinase. *Bacterial Alkaline Phosphatase. *BamH1 Methyltransferase. *BCL-2 Family. *Benzonase. *Beta Glucosidase ...
Role of Aurora A kinase in cancer development and progression.. New anti-tumoral therapies associated with CIN. ...
  • AurKa Pharma is 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. (rwbaird.com)
  • TAM Receptor Kinase Inhibitor, LDC1267, is a cell-permeable, tight-binding "type II" TAM kinase inhibitor (IC₅₀ = 8, 29 & 5 nM for Tyro3, Axl & Mer). (emdmillipore.com)
  • Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression. (uams.edu)
  • Alisertib is an oral inhibitor of the aurora kinase A, a protein involved in cell division that is often overproduced in ovarian and breast cancers and linked with poor prognosis. (ovariancancernewstoday.com)
  • SKIL® (Sareum Kinase Inhibitor Library) is Sareum's drug discovery technology platform that has so far produced the Company's Aurora, VEGFR-3, ALK, FLT3 & TYK2 kinase cancer and auto-immune disease research programmes. (sareum.com)
  • Vichas A, Nkinsi NT, Berger A . Abstract 2726: Functional multiomic profiling identifies Aurora kinase inhibition as a therapeutic strategy inRIT1-mutant lung adenocarcinoma Cancer Research . (academictree.org)
  • Our results provide proof of concept that inhibition of the Aurora B-IN-box interaction is a viable strategy for interfering with CPC function in vivo. (iric.ca)
  • Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. (cusabio.com)
  • Pivotal protein kinases responsible for the massive increase in protein phosphorylation as cells transit into mitosis include Aurora A kinase (AURKA), Aurora B kinase, Polo-like kinase 1 (Plk1), and Cyclin-dependent kinase 1 (Cdk1)/Cyclin A/B complexes. (rupress.org)
  • The hinge (yellow), glycine-rich loop (blue), and activation loop (red) are key features of the protein kinase fold involved in binding adenosine. (wikipedia.org)
  • The protein backbone atoms of residues Glu-211, Ala-213 in the hinge region of Aurora-2, and the sidechain of residue Trp-277, located in the activation loop, bind adenosine through specific hydrogen bonds. (wikipedia.org)
  • Residues Lys-162 and Asp-274 are essential for Aurora-2 kinase activity but do not hydrogen bond to each other as seen in crystal structures of several other protein kinases. (wikipedia.org)
  • protein kinase (AURORA). (ntu.edu.sg)
  • protein kinase (AUR). (ntu.edu.sg)
  • Displays modest selectivity over 39 other protein kinases (at ~1 µM). (emdmillipore.com)
  • Protein kinases and phosphatases complete a central position in the transduction of such signals by way of modulating protein phos phorylation state and activity, hence coordinating subsequent responses. (aurorapathway.com)
  • The importance of protein kinases and phospha tases is demonstrated from the proven fact that 30% of your S. cerevisiae genome is modified by these proteins, selleck though col lectively kinase and phosphatase genes represent only 6% in the genome. (aurorapathway.com)
  • One of the most well studied examples incorporated the mitogen activated protein kinases, which form the phero mone response, filamentous development, the osmotic tension re sponse and cell wall integrity pathways. (aurorapathway.com)
  • The sensing of glucose or pheromones by the G protein coupled recep tors, ends in the activation of your cAMP protein kinase A pathway along with the MAPKs cascade, which influence filamentous growth. (aurorapathway.com)
  • Congratulations to Rob who has won first prize in the #RSCChemBio category of the 2022 #RSCPoster Twitter Conference for his poster on the development of peptidometic inhibitors of the Aurora A/N-Myc Protein-protein interactions. (leeds.ac.uk)
  • Rob Dawber gave the talk 'Investigating key protein-protein interactions of the Aurora-A Kinase' at the BACR & RSC CBBG meeting on 2 December 2021. (leeds.ac.uk)
  • The CPC consists of Aurora B kinase, inner centromere protein (INCENP), and the targeting subunits survivin and borealin/Dasra B. INCENP is a scaffolding subunit for the CPC and activates Aurora B via its conserved IN-box domain. (iric.ca)
  • Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. (cusabio.com)
  • RIO kinases contain a C-terminal RIO domain that is structurally homologous to typical protein kinases. (cancer-research-network.com)
  • Aurora A is a serine/threonine kinase essential for mitotic entry and spindle assembly. (rupress.org)
  • Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have gained a great deal of attention as possible anticancer drug targets. (wikipedia.org)
  • The three Aurora mitotic kinases localize to the centrosome during different phases of mitosis. (aurorapathway.com)
  • 1997). As the last mentioned two are potential Cdk1 focus on sites, the physiological mitotic kinase for S16 continues to be unclear. (sc-26196.com)
  • During mitosis, AKAP95/HA95 recruit HDAC3 along with Aurora B. Subsequently, HDAC3-mediated histone deacetylation facilitates maximal phosphorylation of histone H3 on Ser10 by Aurora B, leading to HP1 dissociation from mitotic chromosomes. (solution-providers-immunotherapies.com)
  • The HDAC3-AKAP95/HA95-Aurora B pathway is required for normal mitotic progression (19). (solution-providers-immunotherapies.com)
  • Histone deacetylase inhibitors (HDACis) have been shown to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) linked to epigenetic changes and epithelial-mesenchymal transition (EMT) state. (nih.gov)
  • Aurora kinase inhibitors are a putative drug class for treating cancer. (wikipedia.org)
  • The Aurora kinase enzymes could be potential targets for novel small-molecule enzyme inhibitors. (wikipedia.org)
  • So far three Aurora-kinase inhibitors have been described: ZM447439, hesperadin and VX-680. (wikipedia.org)
  • Loss of HDAC1 and -2 induces expression of these cyclin-dependent Bambuterol kinase (CDK) inhibitors, leading to a cell cycle block in G1. (solution-providers-immunotherapies.com)
  • citation needed] Kinome Cyclin-dependent kinase Signal transduction Andrews, Paul D. (wikipedia.org)
  • There are three mammalian aurora kinase genes, encoding aurora A, B and C. Intense investigation has focused on aurora A and B as they appear to play a role in oncogenesis with aurora A identified as a low penetrance tumor susceptibility gene in mice and humans. (wikipedia.org)
  • Congratulations to joint Wilson-Bayliss group student Robert Dawber who recently defended his PhD thesis on the topic of peptidomimetic modulators of the interactions of Aurora A with intrinsically disorder proteins. (leeds.ac.uk)
  • 2005), while the Dasra proteins and Survivin can regulate Aurora B localization to centromeres (Carvalho et al. (sc-26196.com)
  • Intracellularly, glucose is phosphorylated by hexo and/or gluco kinases activating Ras2 signalling that also induces the filament ous growth cAMP PKA and MAPK pathways. (aurorapathway.com)
  • Verpelli C, Bertani G, Cea V, Patti M, Bikfalvi A, Bello L, Sala C (2010)Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. (u-bordeaux.fr)
  • Intracellular -catenin amounts are controlled with a complicated made up of axin, casein kinase 1 (CKI)a, and adenomatous polyposis coli (APC). (uitest.info)
  • Furthermore, Aurora kinases are known to be oncogenic and overexpressed in various forms of cancerous growth, including leukemia, colon cancer, prostate cancer and breast cancer tumors. (wikipedia.org)
  • Metformin has AMP-kinase (AMPK) dependent and independent mechanisms of action, most notably affecting the liver and skeletal muscle. (intechopen.com)
  • Aurora kinases regulate cell cycle transit from G2 through cytokinesis, and thus are targets in cancer therapy. (wikipedia.org)
  • SKIL can also generate drug research programmes against other kinase targets. (sareum.com)
  • How Aurora B activity could be governed spatially and usually to regulate such a buy HKI-272 different set of procedures nevertheless remains a superb question. (sc-26196.com)
  • Targeting the INCENP IN-box-Aurora B interaction to inhibit CPC activity in vivo. (iric.ca)
  • Omnia® Kinase Assays utilize a fluorescence peptide substrate-based technology for the rapid, homogenous and sensitive detection of enzymatic activity. (thermofisher.com)
  • Increases in kinase activity result in a corresponding increase in fluorescence. (thermofisher.com)
  • FM-479 is the negative control of FM-381 (HY-102046) and has no activity on JAK3 or other kinases[1]. (csnpharm.cn)
  • The important TOR kinase complexes management cell development and metabolism in response to envir onmental cues. (aurorapathway.com)
  • The dominant-negative effect of soluble IN-box expression depends on residues corresponding to hINCENP W845 and/or F881, suggesting that these are essential for Aurora B binding in vivo. (iric.ca)
  • Recent molecular studies have revealed the existence of multiple, distinct mechanisms of Aurora A activation, each occurring at specific subcellular locations, optimized for cellular context, and primed by signaling events including phosphorylation and oxidation. (rupress.org)
  • This study identified HEF1/NEDD9 as an interactive partner for focal adhesion kinase (FAK), connecting it to integrin signaling. (wikipedia.org)
  • Binding sites for Aurora B, Dasra and Survivin, as well as location of the TSS-motif are shown. (sc-26196.com)
  • Exposure of proliferating WS1 cells to MK-8776 S-isomer is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to MK-8776 S-isomer as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK. (xcessbio.com)
  • Sareum's Chk1 kinase cancer research programme is a joint research collaboration with The Institute of Cancer Research and Cancer Research Technology Limited. (sareum.com)