AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
Cyclic GMP-Dependent Protein KinasesCyclic GMPProtein KinasesPhosphatidylinositol 3-KinasesProtein-Serine-Threonine KinasesMAP Kinase Signaling SystemCyclic GMP-Dependent Protein Kinase Type IProtein Kinase InhibitorsCarbazolesCyclic AMP-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein KinasesProtein-Tyrosine Kinasessrc-Family KinasesProtein Kinase CCDC2 Protein KinaseNitric Oxide DonorsPhosphorylationGuanylate Cyclasep38 Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinase 1Cyclic Nucleotide Phosphodiesterases, Type 5Nitric OxideSignal TransductionOxadiazolesp21-Activated KinasesMitogen-Activated Protein Kinase KinasesJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinase 3Cell Cycle ProteinsCyclin-Dependent KinasesEnzyme InhibitorsCreatine KinaseMAP Kinase Kinase KinasesIndolesEnzyme ActivationeIF-2 KinaseCasein Kinase IICasein KinasesPhosphodiesterase 5 InhibitorsPyruvate KinaseRibosomal Protein S6 Kinasesrho-Associated KinasesMitogen-Activated Protein KinasesMAP Kinase Kinase 1S-Nitroso-N-AcetylpenicillamineReceptor Protein-Tyrosine KinasesThymidine KinasePhosphodiesterase InhibitorsExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase 4QuinoxalinesAlkaloidsThionucleotidesNuclear ProteinsCells, Cultured1-Phosphatidylinositol 4-KinasePhosphotransferases (Alcohol Group Acceptor)MevinphosTransfectionCDC2-CDC28 KinasesBlotting, WesternI-kappa B KinaseKineticsGlycogen Synthase Kinase 3MitosisCalciumAurora KinasesIsoenzymesCyclic AMPProtein Kinase C-deltaProtein Kinase C-alphaProto-Oncogene ProteinsCell LinePhosphoproteinsMutationSulfonesMolecular Sequence DataApoptosisRats, Sprague-DawleyProtein BindingPurinonesCell CycleDiacylglycerol KinaseEnzyme ActivatorsAMP-Activated Protein KinasesTyrosineDose-Response Relationship, DrugProto-Oncogene Proteins c-aktFocal Adhesion Kinase 1G2 PhasePenicillaminePurinesMyosin-Light-Chain KinaseRNA, MessengerCyclin-Dependent Kinase 2Amino Acid SequenceJanus Kinase 2Base SequenceSchizosaccharomyces pombe ProteinsSubstrate Specificity
CheckpointPhosphorylationInhibitorMitosisProtein kinasesRegulatesTyrosineCyclinMitoticArrestCDC2Chk1ApoptosisPhosphorylatesInhibitionRegulatorInhibitorsUpstreamSpindle assemblyProstate cancerOverexpressionMAPKProliferationPolymeraseActivitySIGNALINGCellsAnti inflammatoryCellularSynthesisReplicationCentrosomeTumorAuroraConcentrationsTreatments
Checkpoint10
  • Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
  • Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
  • Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
  • In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
  • The resulting impairment of the G2-M checkpoint would prevent cancer cells from repairing induced DNA damage, considerably enhancing the effect of the DNA damaging therapy and thus optimizing the therapeutic outcome. (almacgroup.com)
  • Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. (arigobio.cn)
  • In oocytes, caffeine induces the dephosphorylation of MPF by inhibiting the transcription factor Myt1 and activity of the G2 checkpoint kinase Wee1, converting inactive MPF into its active form. (molcells.org)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • As local cell density increases, tensile forces on E-cadherin adhesions are reduced, which prompts the accumulation of the G2 checkpoint kinase Wee1 and downstream inhibitory phosphorylation of Cdk1. (ibecbarcelona.eu)
  • Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.com)
Phosphorylation7
  • Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. (arigobio.cn)
  • In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)
  • In addition studies on HeLa cells using Plk1 siRNA interference and overexpression showed that phosphorylation of RSK1 increased upon interference and decreased after overexpression suggesting that Plk1 inhibits RSK1. (biospraysehatalami.com)
  • You can find six phosphorylation sites in RSK1 that are crucial for its activation and its own subsequent part in substrate phosphorylation (21 22 Of the phosphorylation of Ser-380 can be very important to RSK1 activation traveling functions such as for example rules of gene manifestation and protein synthesis and cell cycle regulation as a downstream Nisoxetine hydrochloride kinase in the Mos-MAPK pathway (23). (biospraysehatalami.com)
  • The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. (wikidata.org)
  • mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. (wikidata.org)
  • These concentrations usually do not signifi cantly inhibit ERK phosphorylation on their particular, how ever, they've synergy which has a reduced concentration of CI 1040 at two ?M to inhibit ERK phosphorylation. (cdantigens.com)
Inhibitor9
  • We watch, with much interest, as the Wee1 inhibitor continues through clinical trials with the hope of becoming an effective treatment for cancer patients across the globe. (almacgroup.com)
  • Bang, Yung-Jue 2020-02-07 00:00:00 Background The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. (sagepub.com)
  • Adavosertib (AZD1775) is a first-in-class, potent, selec- Electronic supplementary material The online version of this tive WEE1 inhibitor. (sagepub.com)
  • EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. (jcpjournal.org)
  • 13 The expression of CDK inhibitor p21 is upregulated by activated p53, resulting in the suppression of G2/M transition by the inactivation of cyclin/CDK complex. (jcpjournal.org)
  • Nonetheless, selelck kinase inhibitor you will discover handful of research examining the conse quences of inflammatory gene expression in IR injury. (parp1inhibitor.com)
  • AZ 5704 is a potent and selective ATM kinase inhibitor with IC50 of 0.6 nM. (csnpharm.com)
  • MLN8054 is an aurora kinase inhibitor MLN8054, which is an orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. (xcessbio.com)
  • Auora kinase inhibitor MLN8054 binds to and inhibits Aurora kinase A, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregration, and inhibition of cell proliferation. (xcessbio.com)
Mitosis12
  • Chk1 must inactivate in order for the cell to transition from the G2 phase into mitosis, Chk1 expression levels are mediated by regulatory proteins. (wikipedia.org)
  • During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. (arigobio.cn)
  • Inhibiting WEE1 abrogates G2 cell cycle arrest, resulting The tyrosine kinase WEE1 regulates cyclin-dependent kinase in premature entry into mitosis and leading to aberrantly 1 (CDK1), which drives cells from the G2 phase into mitosis, high CDK2 activity in S-phase cells, with the deregulated and CDK2, which drives cells into and through the S phase DNA replication resulting in replication stress [1, 5]. (sagepub.com)
  • We found that Plk1 suppressed the activity of RSK1 during embryonic mitosis and that Plk1 was inhibited during embryonic diapause and mitotic arrest. (biospraysehatalami.com)
  • The collective outcome of these events is initiation of intra-S phase and G2 checkpoints in response to DNA damage or replication stress and maintenance of chromatin integrity during repair of damaged DNA, prior to entry into mitosis. (wustl.edu)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • By six h immediately after release through the G2 M boundary, nearly all cells have entered mitosis and completed this approach albeit either effectively or unsuccessfully. (parp1inhibitor.com)
  • The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. (wikidata.org)
  • Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2. (wikidata.org)
Protein kinases2
  • Chk1 activation can also be ATR-independent through interactions with other protein kinases such as PKB/AKT, MAPKAPK and p90/RSK. (wikipedia.org)
  • All of these members contain a conserved C-terminal amino acid sequence termed the polo box domain which provides a docking site for certain proteins (1) and a kinase domain which is predicted to activate many protein kinases including Aurora A/B PKA ERK1/2 RSK1/2 Akt/PKB and MEK1 (2). (biospraysehatalami.com)
Regulates2
  • In 1993, Beach and associates initially identified Chk1 as a serine/threonine kinase which regulates the G2/M phase transition in fission yeast. (wikipedia.org)
  • promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. (arigobio.cn)
Tyrosine2
  • The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. (cdantigens.com)
  • Trastuzumab and HER tyrosine kinase inhibitors displayed molecular synergis tic interaction with G28UCM. (cdantigens.com)
Cyclin4
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
  • Researchers postulate that ProstaCaid may affect activity of Cdc2/cyclin B1 kinase by reducing this complex formation. (med-chemist.com)
Mitotic5
  • Activation of Chk1 holds the cell in the G2 phase until ready to enter the mitotic phase. (wikipedia.org)
  • Thus, WEE1 inhibition sensitizes cancers have loss-of-function TP53 mutations, meaning that tumor cells to DNA-damaging chemotherapy and can lead to they become more dependent on the G2/M- and S-phase unstable DNA replication, DNA damage and mitotic catas- checkpoints to halt progression of the cell cycle [3, 4]. (sagepub.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • Monomethyl auristatin E (MMAE, vedotin) is a very potent anti-mitotic agent that inhibits cell division by blocking the polymerisation of tubulin. (xcessbio.com)
Arrest6
  • The WEE-1 kinase is a key regulator of several cell cycle checkpoints including G2/M. WEE-1 inhibition can force cells in a state of arrest to continue the cell cycle, ultimately leading to cell death. (almacgroup.com)
  • Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC50 of PTX and increased G2/M arrest. (bvsalud.org)
  • Following DNA damage, WEE1 inhibits CDK1, leading 1 Introduction to cell cycle arrest and allowing time for DNA repair [4]. (sagepub.com)
  • EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. (jcpjournal.org)
  • At 24 hours, 50 mM and 100 mM quercetin induced G2/M arrest and apoptosis, manifested by the decrease in G2/M-related protiens. (med-chemist.com)
  • When coupled to cAC10, MMAE shows selective cytotoxicity in CD30+ cells, and induces G2/M-phase growth arrest and cell death through the induction of apoptosis. (xcessbio.com)
CDC21
  • Cdc2 could be dephosphorylated by Cdc25C and become inactive or be phosphorylated by protein kinase, such as Wee1, and then converted into an inactive form. (med-chemist.com)
Chk14
  • Chk1 has a N-terminal kinase domain, a linker region, a regulatory SQ/TQ domain and a C-terminal domain. (wikipedia.org)
  • Chk1 impacts various stages of the cell cycle including the S phase, G2/M transition and M phase. (wikipedia.org)
  • ATR phosphorylates the CHK1 which in turn phosphorylates and activates WEE1. (wustl.edu)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
Apoptosis4
  • The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)
  • As anticipated, immediately after a 48 h deal with ment period, OcTMAB induced apoptosis in G2 M syn chronized cells, as evident by an increase within the percentage of cells with 2N DNA written content. (parp1inhibitor.com)
  • IL-24 can inhibit the proliferation of many cancer cells by inducing apoptosis without damaging normal cells. (creative-proteomics.com)
  • It can promote tumor cell apoptosis, inhibit tumor cell growth, inhibit tumor angiogenesis, inhibit tumor cell metastasis, etc., so that it has a wide range of selective anti-tumor effects and immune regulation. (creative-proteomics.com)
Phosphorylates2
  • We discovered that WEE1 kinase phosphorylates histone H2B at Tyr37 in a short window of 30-40 minutes in late S phase. (wustl.edu)
  • WEE1 phosphorylates H2B at Tyr37 upstream of histone cluster 1, Hist1. (wustl.edu)
Inhibition2
  • It also suggests that ProstaCaid inhibits cell growth and survival, at least through the inhibition of AKT and MAPK signaling. (med-chemist.com)
  • This inhibition takes place mainly by interactions and stabilization of IB, and interactions together with the IB kinases. (pka-signal.com)
Regulator1
  • Thus, WEE1, a cell cycle regulator has a dual role as an epigenetic modifier that maintains histone transcript levels. (wustl.edu)
Inhibitors1
  • Currently one of three WEE1 inhibitors in clinical development, the Debio 0123 program was initiated based on the deepened understanding of the DNA damage response (DDR) of cancer cells. (almacgroup.com)
Upstream2
  • We obsevered that WEE1 kinase deposit pY37-H2B epigenetic marks upstream of Hist1 cluster, suppressing global histone transcription in both yeast and mammalian cells. (wustl.edu)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
Spindle assembly1
  • Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)
Prostate cancer2
  • WEE1 kinase has been reported to be aberrantly expressed in melanomas, glioblastoma multiforme (GBMs), triple negative breast cancers (TNBCs) and prostate cancer. (wustl.edu)
  • A recent study shows that MLN8054 sensitizes androgen-resistant prostate cancer to radiation by inhibiting Aurora A kinase, which is associated with sustained DNA double-strand breaks. (xcessbio.com)
Overexpression2
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • Although, their part in EMT remains unclear, overexpression of ei ther ARRB1 or ARRB2 in HeLa cells inhibits NF B medi ated transcription. (pka-signal.com)
MAPK2
  • We uncovered that GO terms for MAP kinase phosphatase exercise and inactivation of MAPK ac tivity had been enriched in GC16. (pka-signal.com)
  • Additional examination of GC16 and GC19 exposed en richment for more pathways broadly linked with cancer and EMT, the majority of which overlap or crosstalk with TNF, MAPK, or EGFR signaling. (pka-signal.com)
Proliferation1
  • In addition, MLN8054 selectively inhibits Aurora A over Aurora B in cultured cells, and inhibits cell proliferation by promoting G2/M accumulation and spindle defects in multiple cultured human tumor cells lines. (xcessbio.com)
Polymerase2
  • NPAT is excluded from binding to the Hist1 cluster because of its inability to recognize pY37-H2B, which in turn inhibits RNA polymerase II (Pol II) recruitment. (wustl.edu)
  • Chloroquine Phosphate is the phosphate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties and inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin. (csnpharm.com)
Activity2
  • Dependence of various cancer cells on WEE1 signaling suggests that targeting epigenetic activity of WEE1 is a viable strategy. (wustl.edu)
  • IL-24 has anti-angiogenic activity and reduces tumor micro vessel density by inhibiting angiogenesis. (creative-proteomics.com)
SIGNALING1
  • We employed TNF as being a proinflammatory cytokine to en hance TGFB induced EMT in our model system, and we discover that genes that propagate TNF signaling are upregulated and strongly enriched in GC16 and GC19. (pka-signal.com)
Cells6
  • Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. (ibecbarcelona.eu)
  • Consequently, dense epithelia contain a pool of cells that are temporarily halted in G2 phase. (ibecbarcelona.eu)
  • These cells are readily triggered to divide following epithelial wounding due to the consequent increase in intercellular forces and resulting degradation of Wee1. (ibecbarcelona.eu)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • Arrestins present elevated expression in differentiated cells and inhibit cellular responses to growth stimuli. (pka-signal.com)
  • In breast cancer, IL-24 inhibits the growth of breast cancer cells through an anti-tumor-bystander effect. (creative-proteomics.com)
Anti inflammatory1
  • Minocycline is a blood brain barrier permeable tetracycline derivative that exhibits anti inflammatory, anti apoptotic and antioxidant properties, and which inhibits neuroinflammation and neurodegeneration within the central nervous technique. (parp1inhibitor.com)
Cellular1
  • We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. (waseda.jp)
Synthesis1
  • It can also down-regulate the synthesis of phosphatidylinositol 3-kinase/protein kinase B, focal adhesion kinase, matrix metalloproteinase 2/9, and inhibit cancer cell invasion and metastasis. (creative-proteomics.com)
Replication2
  • WEE1 in chromatin integrity during replication stress. (wustl.edu)
  • Replication protein A (RPA) coats ssDNA formed during DNA replication and DNA repair which facilitates the localization of ATR kinase to sites of DNA damage. (wustl.edu)
Centrosome1
  • However, this hypothesis has been recently challenged by Tsou and Stearns [ 5 ] who proposed that re-duplication is inhibited by a centrosome-intrinsic block [ 10 ]. (biomedcentral.com)
Tumor2
Aurora3
  • Aurora kinase c. (lookformedical.com)
  • Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)
  • Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers. (xcessbio.com)
Concentrations1
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
Treatments2
  • Treatments such as Debio 0123, which inhibit the DDR, are promising drug candidates as they can enhance the effects of DNA damaging therapies and promote a lethal response. (almacgroup.com)
  • Based on the fact that the cytotoxicity of radiation and many such drugs is due to the induction of damage to DNA, a promising strategy for enhancing the effectiveness of these treatments is to inhibit the pathways for repairing these DNA lesions [ 2 ]. (oncotarget.com)