Kinases in cell cycle cell cycle checkpoints. Medical search. Frequent questions

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
As the eukaryotic cell cycle is a complex process, eukaryotes have evolved a network of regulatory proteins, known as the cell cycle control system, which monitors and dictates the progression of the cell through the cell cycle. (wikipedia.org)
The main mechanism of action of the cell cycle checkpoints is through the regulation of the activities of a family of protein kinases known as the cyclin-dependent kinases (CDKs), which bind to different classes of regulator proteins known as cyclins, with specific cyclin-CDK complexes being formed and activated at different phases of the cell cycle. (wikipedia.org)
The E2F gene family is a group of transcription factors that target many genes that are important for control of the cell cycle, including cyclins, CDKs, checkpoint regulators, and DNA repair proteins. (wikipedia.org)
The three pocket proteins are Retinoblastoma (Rb), p107, and p130, which bind to the E2F transcription factors to prevent progression past the G1 checkpoint. (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)
By phosphorylating substrate proteins, kinases modify the activity, location and affinities of up to 30% of all cellular proteins, and direct most cellular processes, particularly in signal transduction and co-ordination of complex pathways. (wormbook.org)
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)
Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. (nih.gov)
Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. (nih.gov)
Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. (thebiogrid.org)
A cells cycle is positively regulated promoting progress through the stages via the interaction of two classes of proteins found in the cytoplasm. (jove.com)
Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus, and that occurs as a response to the mitotic cell cycle spindle assembly checkpoint. (yeastgenome.org)
Those mechanisms affect which kind of therapies might work once cancer patients relapse on PARP inhibitors, a treatment that stops PARP proteins from repairing DNA damage in cancer cells and leads to cell death. (yale.edu)
8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. (caslab.com)
Here we identified Nup2 in a pool of enriched proteins that co-purify with tagged Ndj1 from meiotic cell extracts. (biorxiv.org)
For E-MDA-MB- 231, down-regulation of catalase, paraoxonase-2 (PON2), clusterin, an inhibitor of apoptosis proteins (IAPs) and cell stress proteins validated the notion that E-cadherin re-expression enhances TZT anti-cancer efficacy. (eurekaselect.com)
Spy1/RINGO (Spy1) proteins bind and activate Cdk but are resistant to canonical regulatory mechanisms that establish cell-cycle checkpoints. (escholarship.org)
The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
Proteins that control the CELL DIVISION CYCLE. (bvsalud.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)

Checkpoint kinase 1 (Chk1, CHEK1) is a Ser/Thr protein kinase that plays a key role in mediating the cellular response to DNA-damage. (rcsb.org)
LY2606368 is a potent and selective ATP competitive inhibitor(IC50=1.5 nM in SW1990 cell) of the Chk1 protein kinase. (chemspider.com)
Most protein kinases share a common ePK (eukaryotic protein kinase) catalytic domain, and can be identified by sequence similarity with Blast or profile hidden Markov models (HMMs). (wormbook.org)
We identified 438 protein kinase genes, including 20 atypical kinases, and an additional 25 kinase fragments or pseudogenes. (wormbook.org)
The protein encoded by this gene belongs to the Ser/Thr protein kinase family. (caslab.com)
Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.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)

Replication blockages activate the ATR kinase which, in turn, activates the downstream effector kinase Chk1 through the mediator protein, Claspin. (caltech.edu)
Chk1 facilitates the arrest of cell cycle progression and the inhibition of replication origin firing. (caltech.edu)
The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. (expasy.org)
SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)

Weighed against its homologs Plk1 (and its own connected signaling pathway) offers attracted much interest because overexpression of Plk1 can be firmly correlated with carcinogenesis (10 11 Furthermore inhibition of Plk1 using RNA disturbance (RNAi) or particular little molecule inhibitors causes development arrest or apoptosis in tumor cells (12-14). (biospraysehatalami.com)
Discovery of a Novel Class of Triazolones as Checkpoint Kinase Inhibitors--Hit to Lead Exploration. (rcsb.org)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.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)
She already has a candidate in mind for the job: a new class of drugs called ATR kinase inhibitors. (yale.edu)
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)
Within a decade of the initial discovery, the development of small molecule kinase inhibitors of BRAF (e.g., vemurafenib and dabrafenib) and their clinical validation occurred, showing significant short-term responses in patients with ERK1 corresponds to C161 in ERK2 and C159 in Rattus norvegicus ERK2. (cell-signaling-pathways.com)

Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. (wikipedia.org)
Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. (wikipedia.org)
Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein. (wikipedia.org)
Those complexes, in turn, activate different downstream targets to promote or prevent cell cycle progression. (wikipedia.org)
Therefore it would be interesting to examine the control mechanism of cell cycle progression in which RSK1 affects Myt1 in meiosis and Plk1 affects Myt1 in mitosis. (biospraysehatalami.com)
Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness. (uc.edu)
Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. (nih.gov)
In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. (nih.gov)
We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. (nih.gov)
A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. (mdpi.com)
Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. (rupress.org)
Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. (nih.gov)
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)
CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)

G 2 /M arrest was associated with DNA damage as indicated by phosphorylation of H 2 A.X at Ser139 and activation of checkpoint kinase 2 (Chk2) in all the three cell lines. (aspetjournals.org)
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)
Here we provide evidence that exogenous DSBs lead to Rad53 phosphorylation during the meiotic cell cycle, whereas programmed meiotic DSBs do not. (unimi.it)
Rad53 phosphorylation/activation is elicited when unrepaired meiosis-specific DSBs escape the recombination checkpoint. (unimi.it)
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)
Additionally, the checkpoint kinases modify the chromatin surrounding DNA damages through phosphorylation of the H2A histone (H2AX in mammals). (cea.fr)
Protein phosphorylation is a reversible and dynamic post-translational modification that is governed by the opposing activities of protein phosphatases and kinases. (rndsystems.com)
β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)

Growth-inhibitory effects of DIM were mediated by cell cycle arrest in G 2 /M phase in all the three cell lines. (aspetjournals.org)
To further establish the involvement of Chk2 in DIM-mediated G 2 /M arrest, cells were transfected with dominant-negative Chk2 (DN-Chk2). (aspetjournals.org)
Blocking Chk2 activation by DN-Chk2 completely protected cells from DIM-mediated G 2 /M arrest. (aspetjournals.org)
These results were further confirmed in Chk2 knockout DT40 lymphoma cells, in which DIM failed to cause cell cycle arrest. (aspetjournals.org)
These results clearly indicate the requirement of Chk2 activation to cause G 2 /M arrest by DIM in ovarian cancer cells. (aspetjournals.org)
Blocking ROS generation by N -acetyl cysteine protects the cells from DIM-mediated G 2 /M arrest and apoptosis. (aspetjournals.org)
The cell cycle checkpoints play an important role in the control system by sensing defects that occur during essential processes such as DNA replication or chromosome segregation, and inducing a cell cycle arrest in response until the defects are repaired. (wikipedia.org)
cell cycle arrest. (biospraysehatalami.com)
Here we show that encysted embryos (cysts) of the primitive crustacean are ideal for such research because they undergo WNT7A complete cell cycle arrest when they enter diapause (a state of obligate dormancy). (biospraysehatalami.com)
however commonly used animal models are limited in that cell cycle arrest must be induced by treatment with drugs. (biospraysehatalami.com)
In this model, 16e was shown to abrogate topotecan-induced cell cycle arrest in a dose dependent manner. (rcsb.org)
Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
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)
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)
The ATR kinase communicates DNA damage to the cell and activates DNA damage checkpoints, which arrest the cell cycle to provide time for repairs. (yale.edu)
It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. (caslab.com)
Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. (nih.gov)
Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
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)
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)
However, THP-1 cells adaptively adjusted to LeTx and overrode cell cycle arrest by activating the PI3K/Akt signaling pathway. (uwo.ca)
Recovery from cell cycle arrest was required before recovering from on-going MEK1 cleavage and suppression of TNF-a production. (uwo.ca)
TG 003 signaling dynamics and to induce cell cycle arrest and apoptosis in ERK-dependent cancers. (cell-signaling-pathways.com)

If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
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)
Aims: The aim of this study was to sensitize the resistant breast adenocarcinoma cells towards Tumour Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced apoptosis. (eurekaselect.com)
Objective: Therefore, this research investigated whether the combination of Trichostatin A (TSA) and Zebularine (Zeb) (TZ) followed by TRAIL (TZT) could sensitize the human breast adenocarcinoma cells towards apoptosis. (eurekaselect.com)
The cells were subjected to hematoxylin and eosin (H & E) staining and FITC-Annexin V/Propidium Iodide apoptosis detection prior to proteome profiling. (eurekaselect.com)
Results: Based on morphological observation, apoptosis was induced in all cells treated with all treatment regimens though it was more evident for the TZT-treated cells. (eurekaselect.com)

Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. (wormbook.org)
Protein kinases constitute one of the largest and most important of protein families, accounting for ~2% of genes in a variety of eukaryotic genomes. (wormbook.org)
Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. (thebiogrid.org)

Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)

By default, CDKs are always present in a cell in an inactivated form. (jove.com)
Positive regulators include two protein groups that allow cells to pass through regulatory checkpoints: cyclins and cyclin-dependent kinases (CDKs). (jove.com)
Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. (kegg.jp)
Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
Cancer cells exploit Spy1 to stimulate proliferation through inappropriate activation of Cdks, yet the mechanism is unknown. (escholarship.org)

Cyclins and cyclin dependent kinases, or CDK. (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)

Genotoxic stress which specifically affects cells in S-phase is detected by the replication checkpoint. (caltech.edu)
The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. (nih.gov)

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)

However, a function for SET8 in mammalian cell proliferation has not been determined. (rupress.org)
We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. (rupress.org)
It inhibits cytokine production and cell proliferation/differentiation in various immune cells. (uwo.ca)
This study demonstrated that modulation of PI3K/Akt/GSK3 signaling cascades can be beneficial for protecting or facilitating recovery from cellular LeTx intoxication in cells that depend on basal MEK1 activity for proliferation. (uwo.ca)

In collaboration with AstraZeneca, Jensen has focused on three BRCA2 reversion alleles, containing deletions in the BRCA2 gene that reactivate DNA repair functions, in tumor cell DNA from ovarian cancer patients who relapsed on a PARP inhibitor. (yale.edu)
In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O 6 -benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. (nih.gov)
This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O 6 -Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells. (nih.gov)
Treatment with the novel cyclophilin inhibitor NV651, presented a potent antiproliferative effect in HCC cell lines via cell cycle perturbations arresting cells in the mitotic phase. (lu.se)
Cell-free DNA in the supernatant of pleural effusion can be used to detect driver and resistance mutations, and can guide tyrosine kinase inhibitor treatment decisions. (cdc.gov)
Participants have received one prior platinum-based chemotherapy and one prior immune checkpoint inhibitor therapy either in combination or in sequence. (who.int)
Exclusion criteria: --Participants who have previously received docetaxel, KRAS G12C inhibitor, or any other systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior immune checkpoint inhibitor therapy. (who.int)

The decision to commit to a new round of cell division occurs when the cell activates cyclin-CDK-dependent transcription which promotes entry into S phase. (wikipedia.org)
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)

and the M (mitosis) phase, during which the duplicated chromosomes (known as the sister chromatids) separate into two daughter nuclei, and the cell divides into two daughter cells, each with a full copy of DNA. (wikipedia.org)
DNA damage checkpoint response to accidental DSBs during mitosis requires the Rad53 effector kinase, whereas the meiosis-specific Mek1 kinase, together with Red1 and Hop1, mediates the recombination checkpoint in response to programmed meiotic DSBs. (unimi.it)
When B levels drop, the cell exits mitosis and divides. (jove.com)

Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. (wormbook.org)
Many of these pathways are highly conserved, and 53 distinct kinase functions and subfamilies appear to have been conserved between yeasts, nematodes, insects and vertebrates, with a further 91 subfamilies of kinases being seen throughout metazoan genomes. (wormbook.org)
Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. (elifesciences.org)
Sensitization of cancer cells to conventional drugs using multi-target agents that block survival and oncogenic pathways, alone or in combination, is an emerging strategy to overcome drug resistance. (researchsquare.com)
The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
LY2157299 enhances anti-tumor effect by disrupting TGF-β-dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. (nih.gov)
Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)

These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
and the metaphase-to-anaphase transition, also known as the spindle checkpoint. (wikipedia.org)
Glc7p functions in opposition to key spindle assembly checkpoint protein Aurora kinase (Ipl1p). (yeastgenome.org)
The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)

Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. (elifesciences.org)
By counteracting the activities of kinases, phosphatases play an important role in the control of a wide variety of cellular functions including cell cycle checkpoints, responsiveness to growth factors, contact inhibition, and cellular motility. (rndsystems.com)
We could confirm the increased polyploidy upon Mps1 inhibition in neuroblastoma cell lines and PDX model, leading to mitotic catastrophe activating the caspase-dependent mitochondrial apoptotic pathway. (lu.se)
Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. (cdc.gov)

The ATM gene encodes a large protein that belongs to a family of kinases possessing a highly conserved C-terminal kinase domain related to the phosphatidylinositol 3-kinase domain. (bmj.com)

Our results establish Chk2 as a potent molecular target of DIM in ovarian cancer cells and provide the rationale for further clinical investigation of DIM. (aspetjournals.org)

Role of the Saccharomyces cerevisiae Rad53 checkpoint kinase in signaling double-strand breaks during the meiotic cell cycle / H. Cartagena-Lirola, I. Guerini, N. Manfrini, G. Lucchini, M.P. Longhese. (unimi.it)
This makes kinase signaling particularly amenable to comparative studies, and kinase activity a particularly good readout of the physiological state of any cell. (wormbook.org)
An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling. (uc.edu)

A further 91 subfamilies were found in all three metazoan kinomes, including the tyrosine kinase (TK) group and the TKL group, which mediate much of the complexity of intercellular signal transduction. (wormbook.org)

Compared to the eukaryotic cell cycle, the prokaryotic cell cycle (known as binary fission) is relatively simple and quick: the chromosome replicates from the origin of replication, a new membrane is assembled, and the cell wall forms a septum which divides the cell into two. (wikipedia.org)

Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
An image depicting head and neck squamous cell carcinoma in vitro can be seen below. (medscape.com)
Head and neck squamous cell carcinoma in vitro (cell culture). (medscape.com)
Our in vitro study demonstrated that sequential treatment of O 6 -Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. (nih.gov)
Consistent with these observations, incubation of the ERK2BI-78D3 adduct (UV spectrum is shown in Supplementary Fig.?15a) with 5?mM glutathione for 30?min failed to rescue the activity of ERK2, as determined using an in vitro kinase assay (Supplementary Fig.?15c). (cell-signaling-pathways.com)
NV556 treatment in an in vitro 3D human liver Extracellular Matrix (ECM) cultured with a TGFβ1-activated human hepatic stellate cell line led to decreased collagen production. (lu.se)

Both the BRCA1 and BRCA2 protein are involved in DNA repair," said Megan King , PhD , associate professor of cell biology and of molecular, cellular and development biology, and co-leader of the Radiobiology and Genome Integrity Research Program at Yale Cancer Center. (yale.edu)
Although older chemotherapeutic drugs are often toxic to normal cells, advances in genetics and cellular and molecular biology have led to development of more selective drugs. (msdmanuals.com)

Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. (tocris.com)
It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
We evaluated the effect of 3,3′-diindolylmethane (DIM) in ovarian cancer cells. (aspetjournals.org)
DIM treatment inhibited the growth of SKOV-3, TOV-21G, and OVCAR-3 ovarian cancer cells in both a dose- and time-dependent manner with effective concentrations ranging from 40 to 100 μM. (aspetjournals.org)
RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. (nature.com)
Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells. (uc.edu)
Martin Reck, MD, PhD, of the LungenClinic, discusses in German study findings on pembrolizumab vs platinum-based chemotherapy as first-line therapy for advanced non-small cell lung cancer with a PD-L1. (ascopost.com)
Giorgio V. Scagliotti, MD, PhD, of the University of Torino, discusses in Italian study findings on ceritinib vs chemotherapy in patients with advanced ALK-rearranged non-small cell lung cancer previo. (ascopost.com)
Our HCC signature covered well-established liver cancer hallmarks, and network analyses revealed coordinated interaction between several MRs. One novel MR, SEC14L2 , exerted an anti-proliferative effect in HCC cells and strongly suppressed tumor growth in a mouse model. (aging-us.com)
We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell. (mdpi.com)
Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. (elifesciences.org)
PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. (elifesciences.org)
Thus, addressing the presence of immunosuppressive myeloid cell populations in the periphery and tumor microenvironment of patients with cancer is likely to be required for effective NK cell-based immunotherapy. (elifesciences.org)
Cancer is characterized as the uncontrolled multiplication and spread of the body's particular cells. (researchsquare.com)
In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
Cancer is characterized by uncontrolled growth and division of a cell, with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
[ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. (nature.com)
First, given evidence that IGFs regulate the response to IR, we also found evidence that IGF-1R depletion induced endogenous DNA lesions marked by γH2AX foci in prostate cancer cells [ 10 ]. (nature.com)
Targeting the cell cycle has been proposed as a therapeutic strategy in cancer treatment with special interest in the mitotic phase. (lu.se)
Загальні відомості про терапію злоякісних новоутворень Curing cancer requires eliminating all cells capable of causing cancer recurrence in a person's lifetime. (msdmanuals.com)
The ideal drug would target only cancer cells and have no adverse effects on normal cells. (msdmanuals.com)
Cytotoxic drugs damage DNA and kill many normal cells as well as cancer cells. (msdmanuals.com)
In contrast, other drugs (eg, DNA cross-linkers, also known as alkylating agents) have a linear dose-response relationship, killing more cancer cells at higher doses. (msdmanuals.com)
Study of efficacy and safety of JDQ443 in comparison with docetaxel in participants with non-small cell lung cancer. (who.int)
A randomized, controlled, open label, phase III study evaluating the efficacy and safety of JDQ443 versus docetaxel in previously treated participants with locally advanced or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC). (who.int)

Taken together these findings provide insights into the regulation of Plk1 during cell division and diapause cyst formation and the correlation between the activity of Plk1 and RSK1. (biospraysehatalami.com)
As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)

Distribution of 212 kinase subfamilies throughout four kinomes: the yeast Saccharomyces cerevisiae , the nematode worm Caenorhabditis elegans , the fruit fly Drosophila melanogaster and human. (wormbook.org)

Finally, we showed that ssDNA lesions are converted to toxic DSBs in cells lacking functional ataxia telangiectasia mutated (ATM), likely due to failure to form 53BP1 bodies and/or a role for ATM in SSB repair or fork protection [ 14 ]. (nature.com)

Because of its mutated aggressive genetics, this cell has a selective growth advantage over its neighbors. (medscape.com)

The integrity of DNA replication control and checkpoint mechanisms is essential for preventing tumorigenesis. (caltech.edu)
Natural killer (NK) cell-based immunotherapy may overcome genetic mechanisms of resistance to T cell-based immunotherapy through antigen- and MHC-independent recognition of malignant cells. (elifesciences.org)
They have complementary mechanisms to hinder the carcinogenic process by searching free radicals, inhibiting survival and multiplication of malignant cells, as well as reducing invasiveness and angiogenesis of tumors. (researchsquare.com)
For chemotherapy drugs, one of the best characterized resistance mechanisms is overexpression of MDR1 , a cell membrane transporter that causes efflux of certain drugs (eg, vinca alkaloids, taxanes, anthracyclines). (msdmanuals.com)

Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. (nih.gov)
We identify mutations in Spy1 that ablate its ability to activate Cdk2 and to proliferate cells. (escholarship.org)

Meiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. (biorxiv.org)

NK cells express germ-line receptors that are either stimulatory or inhibitory, and the summation of these signals determines activation status ( Caligiuri, 2008 ). (elifesciences.org)
Similar trend was observed in MCF-7 whereby TZT treatment down-regulated the anti-apoptotic catalase and PON2, increased the proapoptotic, B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax), second mitochondria-derived activator of caspase (SMAC) and HtrA serine peptidase 2 (HTRA2) as well as TRAIL receptors (TRAIL R1 and TRAIL R2). (eurekaselect.com)

Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)
This system acts like a timer, or a clock, which sets a fixed amount of time for the cell to spend in each phase of the cell cycle, while at the same time it also responds to information received from the processes it controls. (wikipedia.org)
A phase II study showed that patients with resected local-regionally advanced head and neck squamous cell carcinoma (HNSCC) had improved survival when pembrolizumab was added to adjuvant RT (NCT02641093). (nature.com)
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)
Alain Ravaud, MD, PhD, of Bordeaux University Hospital, discusses in French phase III findings on sunitinib vs placebo as adjuvant treatment for high-risk renal cell carcinoma after nephrectomy. (ascopost.com)
When this complex forms the CDK can phosphorylate a target protein which alters it's function and initiates the cell to advance to the next phase. (jove.com)
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)
Checkpoint systems allow the accurate execution of each cell-cycle phase. (ox.ac.uk)

Altogether, these data indicate that Rad53 prevents sister chromatid segregation in the presence of unrepaired programmed meiotic DSBs, thus providing a salvage mechanism ensuring genetic integrity in the gametes even in the absence of the recombination checkpoint. (unimi.it)
CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. (nih.gov)

However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. (nature.com)
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)

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)

DNA replication is initiated by the S-CDK and DDK kinases which mediate the unwinding of the replication fork. (caltech.edu)

p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)

The classification is based on sequence similarity within the kinase domain, the presence of additional domains, known biological functions, and conservation across divergent genomes. (wormbook.org)

We characterized Xenopus Claspin as a kinase substrate of DDK which forms a stable nuclear complex with Cdc7 and Drf1 under both arrested and unperturbed replication conditions. (caltech.edu)

The G1 checkpoint, also known as the restriction point in mammalian cells and the start point in yeast, is the point at which the cell becomes committed to entering the cell cycle. (wikipedia.org)
Four polo family members are present in mammalian cells: Plk1 Plk2/Snk Plk3/Fnk/Prk and Plk4/Sak. (biospraysehatalami.com)
BI-78D3 forms a covalent adduct with ERK in mammalian cells We next evaluated the ability of BI-78D3 to covalently modify C159 of ERK in intact cells. (cell-signaling-pathways.com)

In addition, tumor-associated antigens (TAAs) produced by irradiated tumor cells can be captured by antigen-presenting cells (APCs) in the TME and presented to T cells. (nature.com)
The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)

Activated Akt inhibited GSK3 and prevented proteasome-mediated cyclin D1 degradation in LeTx-intoxicated THP-1 cells. (uwo.ca)

In the present study, I demonstrated that a brief exposure to LeTx caused a continual MEK1 cleavage and prevented TNF-ce production in non-proliferating cells such as human peripheral blood mononuclear cells or mouse primary peritoneal macrophages. (uwo.ca)

Flow cytometric analysis of H2AX (pS139) expression on human peripheral blood mononuclear cells (Right Panel). (bdbiosciences.com)

Since kinases perform such a variety of distinct basic cellular functions, it is not surprising to see that 53 subfamilies and functions are present in all four kinomes ( Figure 1 ). (wormbook.org)

For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)

DNA damage is the main indication for a cell to "restrict" and not enter the cell cycle. (wikipedia.org)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
The combination of NV651 and cisplatin, a DNA damage reagent, resulted in a synergistic effect in cell viability, and a significant increase on cell death in HCC cell lines. (lu.se)

Additionally, NAA20 knockdown decreased the expression of EGFR in TNBC cells. (bvsalud.org)

Participants with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) rearrangement by local testing. (who.int)

Anatomy21

Organisms5

Diseases10

Chemicals and Drugs125

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes84

Disciplines and Occupations1

Information Science3

Health Care3

Proteins22

Protein kinase7

Chk18

Inhibitors7

Progression16

Phosphorylation9

Arrest24

Apoptosis8

Genes3

Control Kinases2

CDKs6

Cyclins3

Replication checkpoint2

Cyclin-depend1

Proliferation4

Inhibitor7

Activates2

Mitosis3

Pathways8

Spindle4

Inhibition4

Phosphatidylinositol1

Chk21

Signaling3

Tyrosine1

Eukaryotic cell cycle1

Vitro6

Biology2

Cancer31

Regulation2

Saccharomyces1

Ataxia1

Genetics1

Mechanisms4

Activate2

Meiosis1

Receptors2

Phase8

Genetic2

Immune2

Regulatory1

Mediate1

Targets1

Divergent1

Substrate1

Mammalian3

Tumor cells2

Degradation1

Mek11

Human peripheral blood mononuclear cells1

Cellular1

Phases1

Damage3

Additionally1

Mutation1