• Thus, levels of the four different cyclins vary in predictable patterns and combine with consistent CDKs at specific points to achieve forward momentum. (jove.com)
  • Positive regulators include two protein groups that allow cells to pass through regulatory checkpoints: cyclins and cyclin-dependent kinases (CDKs). (jove.com)
  • A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [ 2 - 4 ]. (biomedcentral.com)
  • Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). (ox.ac.uk)
  • Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
  • The G1 checkpoint is regulated by a multitude of molecules such as the retinoblastoma family of proteins, cyclins, cyclin dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CDKis). (temple.edu)
  • When unreplicated or damaged DNA is present, cell cycle checkpoint pathways cause cell cycle arrest by inhibiting cyclin-dependent kinases (Cdks). (vt.edu)
  • In the absence of active Chk1, Cdc25A activates cyclin dependent kinases (Cdks) allowing the cell to progress into S or M phase. (vt.edu)
  • Targeting cyclin dependent kinases (CDKs) and cell cycle checkpoint proteins can induce cell cycle arrest and apoptosis in cancer cells. (ucc.ie)
  • It interacts with a site on tubulin that's not affected by cyclin-dependent kinases (CDKs) or mitotic spindle checkpoint proteins. (sunquicksf.com)
  • Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
  • 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)
  • This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and thus may be involved in controlling the timing of mitosis. (wikipedia.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)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • The model was updated with additional interactions, such as those including Myt1, a second inhibitor kinase, and lamin proteins, which become phosphorylated at the onset of nuclear envelope breakdown (NEB) at entry into mitosis. (vt.edu)
  • These genes encode for closely related GTPase proteins responsible for signal transduction within two main pathways, the mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase pathways, involved in the regulation of cell growth, survival, and differentiation. (oaepublish.com)
  • Cell-cycle kinases DDK and CDK are needed upstream for the activation from the MCM complicated and several PGE1 ic50 research have defined the checkpoint-dependent phosphorylation of MCM proteins [24C27], although certain requirements or results for these adjustments for activity or stability from the helicase still stay unclear. (ampkpathway.com)
  • Spy1/RINGO (Spy1) proteins bind and activate Cdk but are resistant to canonical regulatory mechanisms that establish cell-cycle checkpoints. (escholarship.org)
  • 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. (bvsalud.org)
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (ox.ac.uk)
  • We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
  • Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors. (ox.ac.uk)
  • This cycle is primarily regulated by cyclin-dependent kinase (CDK)-cyclin complexes, checkpoint kinases, and CDK inhibitors. (medicalnotes.info)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
  • Background Hormone receptor (HR)-positive breast cancer is a disease for which no immune checkpoint inhibitors have shown promise as effective therapies. (bmj.com)
  • Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors synergistically increased the effectiveness of antiprogrammed cell death protein-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibodies in preclinical studies. (bmj.com)
  • 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)
  • Cyclins and cyclin dependent kinases, or CDK. (jove.com)
  • Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. (lu.se)
  • CAOV3 cells, which are atRA sensitive, have been shown to express p16INK4a (p16), a cyclin dependent kinase inhibitor regulating the G1 checkpoint. (temple.edu)
  • His DNA damage research includes elements of Nuclear export signal, Cell cycle checkpoint, Cyclin-dependent kinase 1, Cyclin B1 and Molecular biology. (research.com)
  • The activation of Chk1 by two time-dependent events in the cell cycle, the critical nuclear to cytoplasmic (N/C) ratio and the cyclin E/Cdk2 maternal timer are explored in this study. (vt.edu)
  • Our broad research interest lies in studying the functions of chromatin remodelers during meiotic chromosome segregation, understanding the single-molecule dynamics of the mitotic kinases such as aurora kinases, cyclin-dependent kinase 1, polo kinases, checkpoint regulators etc. during mitosis, exploring the mechanism of epigenetic transcription memory/mitotic bookmarking and understanding how the mitotic to meiotic transition is achieved at the level of 3D genome organization, kinetochore composition and transcriptome. (mehtalab-iith.com)
  • The Chk1 kinase and its main upstream activator kinase, ATR, are essential checkpoint effectors in response to a wide variety of genotoxic tensions, and inhibit source firing by focusing on the replication kinases, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) [21], while Chk2 and its main upstream activator ATM are primarily associated with the cellular response to double-strand DNA breaks [22]. (ampkpathway.com)
  • The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. (oaepublish.com)
  • N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. (elifesciences.org)
  • E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. (ox.ac.uk)
  • The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. (ox.ac.uk)
  • Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • The focus of this study is the role of protein kinase Chk1 and the phosphatase Cdc25A in the DNA replication checkpoint. (vt.edu)
  • In order to understand the function and regulation of Chk1 in checkpoints, the features of the MBT that activate Chk1 must be identified. (vt.edu)
  • In addition, embryos were injected with Δ34Xic cyclin E/Cdk2 inhibitor, in order to disturb the maternal timer and tested for Chk1 activation and Cdc25A degradation. (vt.edu)
  • Both Chk1 and Cdc25A were unaffected by the disruption of the cyclin E/Cdk2 maternal time in the embryo. (vt.edu)
  • Therefore, the N/C ratio and the cyclin E/Cdk2 maternal timer do not affect Chk1 activation and therefore Cdc25A degradation. (vt.edu)
  • Whereas Chk1 and Chk2 have been reported to be involved in unique signaling pathways originally, there is certainly installation proof for a thorough crosstalk between ATR-Chk1 and ATM-Chk2 controlled checkpoint replies [23]. (ampkpathway.com)
  • Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. (ox.ac.uk)
  • 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)
  • KRAS is regulated by tyrosine kinase receptors and, in turn, activates the MAPK signaling pathway that is mainly involved in determining cell survival, leading to a strong promotion of cell growth and replication. (oaepublish.com)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.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)
  • 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)
  • 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)
  • After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. (jove.com)
  • In Xenopus laevis, early embryonic development consists of twelve rapid cleavage cycles between DNA replication (S) and mitosis (M) without checkpoints or gap phases. (vt.edu)
  • The checkpoint original model represents the activity of Cdc25 phosphatase on the mitosis promoting factor (MPF) that leads the cell into mitosis. (vt.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 is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase. (lu.se)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
  • Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.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)
  • In human monocytic cell lines U-937 and THP-1, LeTx induced cell cycle arrest in Go-Gi phase by rapid down-regulation of cyclin D1/D2 and checkpoint kinase 1 through MEK1 inhibition. (uwo.ca)
  • Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for: 1) CAPN7 recruitment to midbodies, 2) efficient abscission, and 3) NoCut checkpoint arrest. (elifesciences.org)
  • This checkpoint control is critical to avoid genomic instability, and mutations in PGE1 ic50 checkpoint genes are often associated with malignancy [19,20]. (ampkpathway.com)
  • At these checkpoints, positive and negative regulators promote or inhibit a cell's continuation through the cell cycle. (jove.com)
  • The findings imply two integrin-regulated checkpoints in the ERK cascade: the regulation of growth factor activation of ERK and the accumulation of active ERK in the nucleus. (rupress.org)
  • One goal of this work is to understand the developmental role and regulation of checkpoint signaling pathways due to its monitoring of DNA integrity within the cell. (vt.edu)
  • For instance, during G1, when one type of cyclin, named D, is synthesized and binds to a CDK, the cell transitions into S phase, as another cyclin, E, peaks and forms a complex with CDK to promote DNA replication. (jove.com)
  • Internal regulatory checkpoints ensure that a cell's size, energy reserves, and DNA quality and completeness are sufficient to advance through the cell cycle. (jove.com)
  • Cyclins can be categorized as G 1 , G 1 /S, S, or M cyclins based on the cell cycle phase or transition they are most involved in. (jove.com)
  • Generally, levels of a given cyclin are low during most of the cell cycle but abruptly increase at the checkpoint they most contribute to (G 1 cyclins are an exception, as they are required throughout the cell cycle). (jove.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)
  • 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)
  • In some cell types, forced activation of ERK induces cyclin D1 expression in the absence of adhesion, while in other cell types ERK activation alone is not sufficient to induce cyclin D1 expression. (rupress.org)
  • Cell type-specific differences in the stringency of the second checkpoint could explain the contradictory results in earlier studies of ERK signaling. (rupress.org)
  • Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
  • During the cell cycle, there are two main checkpoints that regulate entrance into S and M phases. (vt.edu)
  • Another means of characterizing the unreplicated DNA checkpoint is through the use of mathematical modeling of the checkpoint-signaling cascade of the cell cycle. (vt.edu)
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. (wikipedia.org)
  • Activated Akt inhibited GSK3 and prevented proteasome-mediated cyclin D1 degradation in LeTx-intoxicated THP-1 cells. (uwo.ca)
  • We previously showed that the ESCRT-III subunit IST1 binds the cysteine protease CAPN7 (Calpain-7) and that CAPN7 is required for both efficient abscission and NoCut checkpoint maintenance (Wenzel <i>et al. (elifesciences.org)
  • E is then degraded by cytoplasmic enzymes and cyclin A concentrations increase throughout the S phase and remain high into G2 to promote entry into the M phase when in an active complex. (jove.com)
  • Therefore, the unreplicated DNA checkpoint model was updated with new interactions and experimental data while still preserving previously identified dynamic characteristics of the system. (vt.edu)
  • describe an additional integrin-regulated checkpoint in the activation of extracellular signal-regulated kinases (ERK) by growth factors. (rupress.org)
  • Previous work has shown that integrin-mediated anchorage stimulates growth-factor-mediated activation of ERK and increases in cyclin D1 levels, but activating ERK directly in the absence of integrin engagement gives conflicting results. (rupress.org)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • Kinase activity, which have a strong connection to Oxidative stress. (research.com)
  • CAPN7 proteolytic activity is also required for abscission and checkpoint maintenance. (elifesciences.org)
  • 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)
  • Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
  • Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. (ox.ac.uk)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)