• This conversion is promoted by the double inhibition (i.e., 2i) of mitogen-activated protein kinase kinase (Map2k), antagonizing Fgf signaling, and of glycogen synthase kinase 3 (Gsk3), stimulating the Wnt pathway. (bioone.org)
  • The Xenopus, Drosophila, and Caenorhabditis elegans genomes, on the other hand, contain orthologues only to Aurora A and Aurora B. In all studied species, the three Aurora mitotic kinases localize to the centrosome during different phases of mitosis. (wikipedia.org)
  • Aurora A and Aurora B kinases play important roles in mitosis. (wikipedia.org)
  • Finally, Aurora A helps orchestrate an exit from mitosis by contributing to the completion of cytokinesis- the process by which the cytoplasm of the parent cell is split into two daughter cells. (wikipedia.org)
  • Though the exact mechanism by which Aurora A aids cytokinesis is unknown, it is well documented that it relocalizes to the mid-body immediately before the completion of mitosis. (wikipedia.org)
  • kinase in candida, is an important mitosis regulatory proteins encoded on human being chromosome 20q13.2 that induces oncogenic change followed with centrosome amplification and aneuploidy when over indicated SEMA3E in rodent cells and (6-8). (arcillaresearch.com)
  • Human cancer cells are usually seen as a changes in the amount or organization of DNA because of mistakes in mitosis, causing chromosome instability and aneuploidy. (survivinpathway.com)
  • Development through mitosis depends upon three major regulatory systems, each involving several serine/threonine kinases, referred to as mitotic kinases. (survivinpathway.com)
  • Within this review, we summarize the functions that all of the Aurora kinases has in cancer biology and mitosis, and discuss the binding modes of Aurora A kinase inhibitors, the spot elements in the binding sites and the fortunate inhibitor components. (survivinpathway.com)
  • Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. (oncotarget.com)
  • Mitosis is usually a dynamic process controlled by the activity of multiple kinases with attendant modification of proteins facilitating rigid checkpoint control. (ap26113.com)
  • GSK1904529A Aurora A is found at centrosomes in early mitosis and controls centrosome maturation centriole separation and chromosome alignment (33) whereas accurate targeting of Aurora B to the chromosomes and then to the spindle midzone and midbody is essential for maintaining microtubule/kinetochore attachments and therefore faithful chromosomal segregation (34). (ap26113.com)
  • GR phosphorylation by an Aurora kinase-dependent pathway provides the mechanism explaining the tight coupling GSK1904529A of ligand-independent GR phosphorylation to cell cycle phase because the maximal activity of these kinases occurs in mitosis. (ap26113.com)
  • Böhly, N., Kistner (Hennecke), M. & Bastians, H. Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis. (for2800.de)
  • Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene. (wikipedia.org)
  • Aurora A is a member of a family of mitotic serine/threonine kinases. (wikipedia.org)
  • Serine/threonine protein kinase Aurora B gene plays a regulatory role from G2 to cytokinesis, encompassing key cell cycle events such as centrosome duplication, chromosome bi-orientation, and segregation. (irdrjournal.com)
  • Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
  • Dual specificity protein phosphatase 4 (DUSP4) is a critical negative regulator of the mitogen-activated protein kinase (MAPK) pathway and is often deleted or epigenetically silenced in tumors. (biomedcentral.com)
  • In this study, a new UHPLC-MS/MS method was developed and validated to quantitate a new pan Aurora kinase inhibitor still in preclinical development, SCH-1473759. (usuhs.edu)
  • Therapeutic inhibition of Aurora kinase showed great promise as a probable anticancer regime because of its important role during cell division. (irdrjournal.com)
  • Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • Aurora A also assures proper organization and alignment of the chromosomes during prometaphase. (wikipedia.org)
  • This article discusses the application of mathematics to the cure of cancer, the possible use of systems of smart drugs to perform simple mathematical calculations to identify and kill cancer cells, and presents a possible mechanism, developed by the author several years ago, to selectively destroy cells with abnormal numbers of chromosomes ( aneuploidy ), something common in many forms of cancer. (mathblog.com)
  • Errors in this process lead to the production of cells with an abnormal number of chromosomes or aneuploidy, and this is a major cause of miscarriages and birth defects in humans such as Down syndrome. (jhu.edu)
  • Although there is evidence to suggest that Aurora C might be a chromosomal passenger protein, the cellular function of it is less clear. (wikipedia.org)
  • In the absence of Aurora A mad2, a protein that normally dissipates once a proper kinetochore-microtubule connection is made, remains present even into metaphase. (wikipedia.org)
  • We studied the involvement of protein kinases A and C, phospho inositol 3 kinase, extracellu lar regulated kinases , vesicular release of dopamine, and changes in intracellular Ca2 concentra tions in the actions of estrogens. (inhibitorkit.com)
  • The Aurora kinases really are a group of three highly homologous Ser/ Thr protein kinases, including Aurora A, B and C. (survivinpathway.com)
  • Kim, Y. *, Holland, A.J.*, Lan, W., and Cleveland, D.W. (2010) Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E. Cell 142, 444-455 *Contributed equally. (jhu.edu)
  • cAMP-dependent protein kinase (PKA) signaling is impaired in the diabetic heart. (omrf.org)
  • Bae KM, Wang H, Jiang G, Chen MG, Lu L, Xiao L. Protein kinase C epsilon is overexpressed in primary human non-small cell lung cancers and functionally required for proliferation of non-small cell lung cancer cells in a p21/Cip1-dependent manner. (famri.org)
  • Since the discovery of Polo kinase in Drosophila in 1988 [ 1 ], the Polo-like kinase (Plk) family has been attracting enormous attention, both in academia and in pharmaceutical industry. (oncotarget.com)
  • In the case of the former, it has been suggested that Aurora A cooperates with the kinase Nek2 in Xenopus to dissolve the structure tethering the cell's centrosomes together. (wikipedia.org)
  • It is speculated that Aurora B cooperates with Aurora A to complete this task. (wikipedia.org)
  • The kinase discovered, Eg2, is now referred to as Aurora A. However, Aurora A's meiotic and mitotic significance was not recognized until 1998. (wikipedia.org)
  • Brandt, J.N., Hussey, K.A., and Kim,Y. (2020) Spatial and temporal control for targeting Polo-like kinase during meiotic prophase . (jhu.edu)
  • KIT is a receptor tyrosine kinase type III, which binds to stem cell factor. (inhibitorkit.com)
  • Receptor tyrosine kinases (RTKs) convey pro-tumorigenic responses in breast, colon, lung, and prostate cancer. (utexas.edu)
  • We focus on a group of proteins known as JNK (c-Jun N-terminal Kinases) which are activated by receptor tyrosine kinases in breast cancer models. (utexas.edu)
  • Aurora Kinase-A gene is usually amplified and overexpressed in lots of human malignancies, including colorectal, breasts, ovarian, bladder, gastric and pancreatic malignancies. (arcillaresearch.com)
  • In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
  • Aurora A is critical for proper formation of mitotic spindle. (wikipedia.org)
  • Furthermore, Aurora A is necessary for the proper separation of the centrosomes after the mitotic spindle has been formed. (wikipedia.org)
  • Without Aurora A, the mitotic spindle, depending on the organism, will either never separate or will begin to separate only to collapse back onto itself. (wikipedia.org)
  • Loss of mitotic regulation is a possible cause of aneuploidy in human epithelial malignancy and it is thought to create an abnormal nuclear morphology in cancer cells. (irdrjournal.com)
  • p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
  • Background Aurora kinase A (AURKA) is amplified with varying occurrence in multiple human being cancers including mind and throat squamous cell carcinoma (HNSCC). (arcillaresearch.com)
  • The overexpression of Aurora B has been observed in several tumour types, and has been linked with a poor prognosis for cancer patients. (irdrjournal.com)
  • Therefore, without proper expression of Aurora A, the cell's centrosomes are never able to separate. (wikipedia.org)
  • For example, deletion of Aurora A in C. elegans results in an initial separation of the cell's centrosomes followed by an immediate collapse of the asters. (wikipedia.org)
  • Aurora A is activated by one or more phosphorylations and its activity peaks during the G2 phase to M phase transition in the cell cycle. (wikipedia.org)
  • Inhibiting MLL1 activity or mutating Borealin K143 to arginine perturbs CPC phase separation, reduces Aurora kinase B activity, and impairs the resolution of erroneous kinetochore-microtubule attachments and sister-chromatid cohesion. (carislifesciences.com)
  • Intriguingly, abolishment of Aurora A through RNAi interference results in different mutant phenotypes in different organisms and cell types. (wikipedia.org)
  • This creates an environment for increased rapid bioavail ability of E2 which can elicit nongenomic effects such as Ca2 mobilization, kinase activation, and alterations in dopamine subcellular location via membrane estrogen receptors. (inhibitorkit.com)
  • Our report on the reported chemical scaffolds of Aurora A kinase inhibitors and their binding modes could give a of good use Letrozole ic50 framework from which new design strategies for inhibitors may be evaluated or produced. (survivinpathway.com)
  • The extensive pre-clinical data supports the develop-ment of focused Aurora kinase inhibitors in certain tumefaction types. (survivinpathway.com)