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Checkpoint Kinase 2Cyclic GMP-Dependent Protein KinasesProtein KinasesProtein-Serine-Threonine KinasesCell Cycle ProteinsDNA DamageAtaxia Telangiectasia Mutated ProteinsGenes, cdcG2 PhaseM Phase Cell Cycle CheckpointsMitosisPhosphorylationCell CycleProtein Kinase InhibitorsCell Cycle CheckpointsS PhaseCyclic GMPcdc25 PhosphatasesPhosphatidylinositol 3-KinasesDNA ReplicationHydroxyureaSaccharomyces cerevisiae ProteinsCDC2 Protein KinaseSpindle ApparatusMAP Kinase Signaling SystemSchizosaccharomyces pombe ProteinsSchizosaccharomycesG2 Phase Cell Cycle CheckpointsCyclic GMP-Dependent Protein Kinase Type ISignal TransductionMutationDNA-Binding ProteinsNuclear ProteinsCarbazolesIntracellular Signaling Peptides and ProteinsS Phase Cell Cycle CheckpointsKinetochoresTumor Suppressor ProteinsSaccharomyces cerevisiaeDNA RepairEnzyme ActivationCyclic AMP-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein KinasesProtein-Tyrosine KinasesCell Line, Tumorsrc-Family KinasesNocodazoleProtein Kinase CHeLa CellsRadiation, IonizingEnzyme InhibitorsCyclin-Dependent KinasesApoptosisProtein BindingTumor Suppressor Protein p53Cdc20 ProteinsCell LineMethyl MethanesulfonateNitric Oxide Donorsp38 Mitogen-Activated Protein KinasesDNA Breaks, Double-StrandedAurora KinasesG1 PhaseGuanylate CyclaseRNA, Small InterferingModels, BiologicalMolecular Sequence DataFungal ProteinsUltraviolet RaysCyclin BMitogen-Activated Protein Kinase 1AlkaloidsChromosome SegregationDNA, FungalBlotting, WesternHistonesGenomic InstabilityCyclic Nucleotide Phosphodiesterases, Type 5Nitric OxideAmino Acid SequenceMitogen-Activated Protein Kinase KinasesOxadiazolesProtein Structure, TertiaryJNK Mitogen-Activated Protein Kinasesp21-Activated KinasesRNA InterferenceMitogen-Activated Protein Kinase 3Cell DivisionTransfectionCells, CulturedGamma RaysSerinePhosphoproteinsIndolesStaurosporineReplication Protein AMAP Kinase Kinase KinasesCell SurvivalCreatine KinaseCasein Kinase II
Cyclin-dependWEE1 G2Mitogen-activaSerineMitosisDownstreamPhosphorylationImmune checkpoint blockadeChk1ArrestInteractsIntra-S-phase checkpointSubunitAssembly checkpointChk2CDKsInhibitorProteinsMAPKRegulatorGeneCaseinOncogeneTumorInducesPathwayCdk1PhasesSpindle assemblyReplicationRegulatesCentrosomeProgressionTransitionCatalyticAuroraPhaseDamageSymbolTargetsMechanismCells
Cyclin-depend6
  • Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. (bioone.org)
  • cyclin dependent kinase 1 [Source:HGNC Sym. (gsea-msigdb.org)
  • Most benefits were demonstrated in cyclin dependent-kinase 12 ( CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. (bjbms.org)
  • 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)
  • 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)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
WEE1 G21
Mitogen-activa1
  • HealthDay News) - The mitogen-activated protein kinase (MAPK) p90 ribosomal S6 kinase (RSK) appears to play a role in the poor response of melanoma cells to DNA-damaging agents, according to research published online Oct. 29 in Oncogene . (cancertherapyadvisor.com)
Serine10
  • BUB1 mitotic checkpoint serine/threonine k. (gsea-msigdb.org)
  • Check point kinase 1 (Chk1) is a serine / threonine protein kinase and a key mediator in the DNA damage-induced checkpoint network. (biovendor.com)
  • CK2 (casein kinase 2) is a serine/threonine-selective protein kinase that has been involved in a variety of cellular processes such as DNA repair, cell cycle control and circadian rhythm regulation. (biomedcentral.com)
  • CK2 (casein kinase 2) is an ubiquitously expressed and highly conserved serine/threonine protein kinase that forms a tetramer containing two catalytic (α and/or α´) subunits and two regulatory β subunits [ 1 ]. (biomedcentral.com)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.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)
  • Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A-related kinase 2. (umbc.edu)
  • Serine/Threonine Kinases (STKs), Never In Mitosis gene A (NIMA)-related kinase 2 (Nek2) subfamily, catalytic (c) domain. (umbc.edu)
Mitosis7
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • DSBs are first detected and signaled by the DNA damage checkpoint that triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. (cea.fr)
  • Inhibition of DNA-PKcs activity via a small interfering RNA or a kinase inhibitor results in mitosis delay, abnormal spindle formation, and chromosome misalignment. (amegroups.org)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B 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)
  • The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. (umbc.edu)
Downstream5
  • 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)
  • 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)
  • Once recruited to DSB, these complexes get activated and induce the phosphorylation of numerous targets including transducing kinases, which subsequently phosphorylate downstream effectors to delay cell cycle and promote DNA repair. (cea.fr)
  • RSK was found to be the main protein kinase operating downstream of mitogens and oncogenes of the Ras/MAPK pathway, and, in melanoma, RSK constitutively phosphorylated Chk1. (cancertherapyadvisor.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)
Phosphorylation4
Immune checkpoint blockade4
  • T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
  • Moreover, STING loss prevented the regression of abscopal tumours in the context of ionizing radiation and immune checkpoint blockade in vivo . (nature.com)
  • These findings implicate temporal modulation of the cell cycle as an important consideration in the context of therapeutic strategies that combine genotoxic agents with immune checkpoint blockade. (nature.com)
  • In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. (biomedcentral.com)
Chk16
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • Chk1 is an evolutionarily conserved protein kinase that functions to ensure genomic integrity upon genotoxic stress. (biovendor.com)
  • When the G2 or S checkpoint is abrogated by the inhibition of Chk1, p53- deficient cancer cells undergo mitotic catastrophe and eventually apoptosis, whereas normal cells are still arrested in the G1 phase. (biovendor.com)
  • In in-vivo and in-vitro experiments, RSK phosphorylated checkpoint kinase 1 (Chk1) at Ser280, an inhibitory site. (cancertherapyadvisor.com)
  • RSK promoted silencing of the G2 DNA damage checkpoint in a Chk1-dependent manner. (cancertherapyadvisor.com)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
Arrest3
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. (oncotarget.com)
  • We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. (muni.cz)
Interacts1
  • It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. (umbc.edu)
Intra-S-phase checkpoint1
  • Knocking out SOG1 in the fast weel background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint. (muni.cz)
Subunit3
  • Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
  • The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key component of the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSB) repair and is required for cellular resistance to ionizing radiation (IR) ( 1 , 2 ). (amegroups.org)
Assembly checkpoint1
  • We report that CK2 is essential for porcine oocyte meiotic maturation by regulating spindle assembly checkpoint (SAC). (biomedcentral.com)
Chk21
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
CDKs1
  • Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. (oncotarget.com)
Inhibitor1
  • 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)
Proteins4
  • Indeed in S and G2 phase, RPA binding to 3' single strand overhangs facilitates the recruitment of proteins of the Rad52 epistasis group, among which Rad51, which carries out the strand-exchange reaction. (cea.fr)
  • It seems now clear that posttranslational modification of both DNA repair and checkpoint proteins is of importance for the regulation of their activities but how these modifications are regulated and how they affect the activity of the proteins only begins to be described. (cea.fr)
  • 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)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
MAPK1
  • The researchers found that MAPK-activated protein kinase RSK played a role in melanoma chemoresistance by altering the response to chemotherapeutic agents. (cancertherapyadvisor.com)
Regulator1
Gene1
  • 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)
Casein1
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
Oncogene1
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
Tumor4
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
  • The tumor suppressor protein p53 is inhibition also exploits the G1 checkpoint deficiency seen involved in regulation of the G1 checkpoint. (sagepub.com)
  • 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)
  • 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. (lookformedical.com)
Induces2
  • 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)
  • Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. (elifesciences.org)
Pathway1
  • In general, NHEJ is the preferred pathway in the G1 phase of the cell cycle, while HR is favored in S and G2 phases. (cea.fr)
Cdk11
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
Phases1
  • JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. (bioone.org)
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)
Replication2
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • Resection is accompanied by the binding of replication protein A (RPA) to the 3' single-stranded overhangs, which helps recruiting the checkpoint complexes. (cea.fr)
Regulates1
  • Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. (umbc.edu)
Centrosome1
Progression2
  • Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. (ibecbarcelona.eu)
  • These findings provide evidence that, in mature T lymphocytes, cell-cycle progression through the G 2 -M check point requires expression of the Src-family protein tyrosine kinase, Lck. (uaeu.ac.ae)
Transition1
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
Catalytic1
  • The Nek family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)
Aurora4
Phase4
  • Consequently, dense epithelia contain a pool of cells that are temporarily halted in G2 phase. (ibecbarcelona.eu)
  • Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. (princeton.edu)
  • Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. (princeton.edu)
  • Checkpoint systems allow the accurate execution of each cell-cycle phase. (ox.ac.uk)
Damage3
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • These checkpoints act as molecular brakes on immune cells, preventing excessive activation and potential damage to healthy tissues. (biomedcentral.com)
Symbol1
Targets1
  • p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)
Mechanism1
  • One such mechanism involves the upregulation of immune checkpoints, such as programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), cluster of differentiation 86 (CD86)/cytotoxic T-lymphocyte antigen 4 (CTLA-4) [ 16 ]. (biomedcentral.com)
Cells1
  • However, cancer cells exploit these checkpoints to evade immune surveillance and suppress antitumor immune responses. (biomedcentral.com)