Kinases m phase cell cycle checkpoints. Medical search. Frequent questions

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)
Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.org)
The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
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)
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)
I'm using cell and molecular biology techniques, biochemistry as well as microscopy to characterise the plant SUN proteins. (brookes.ac.uk)
This includes finding out what other proteins the SUNs bind to and what functions they have during cell division. (brookes.ac.uk)
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)
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)
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)
Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
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)
Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
The role of cell cycle checkpoint proteins is to integrate internal and external factors to determine whether the cell is prepared for progression of the cell cycle. (ptgcn.com)
The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm. (ptgcn.com)
Cyclin-dependent kinases and tumor suppressor proteins are stimulators and modulators of cell division. (ptgcn.com)
The key role of checkpoint proteins is to detect DNA damage and send a signal to delay cell cycle advance until the damaged chromosomes are repaired (Figure 1). (ptgcn.com)
Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). (biomedcentral.com)
The oocyte is loaded with maternal mRNAs and proteins that control the cell maintenance and fate and the formation of the body plan prior to the onset of zygotic genome expression [ 3 , 4 ]. (biomedcentral.com)
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)

Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
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)
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). (salesandmarketingnetwork.com)
SRA141 is a potent, selective, orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7). (salesandmarketingnetwork.com)
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)
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)
Due to a defect in HR, all HPV positive cell lines were efficiently radiosensitized by the PARP-1 inhibitor olaparib. (oncotarget.com)
CAOV3 cells, which are atRA sensitive, have been shown to express p16INK4a (p16), a cyclin dependent kinase inhibitor regulating the G1 checkpoint. (temple.edu)
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)

At these checkpoints, gatekeeper molecules block or allow events, depending on their level of phosphorylation. (wikipedia.org)
Cdc2, part of the metaphase entry checkpoint, is active depending on the pattern of phosphorylation. (wikipedia.org)
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)
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)
β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)
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)
FANCD2 is a phosphorylation target of kinases ATM and perhaps ATR, a phosphorylation that is necessary to maintain the S-phase checkpoint. (kupferlab.org)

Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. (kegg.jp)
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)
They are able to build complexes with cyclin-dependent kinases (CDKs) and regulate their activity ( 2 ). (iiarjournals.org)
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)

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)
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)
Chk1 regulates cell cycle arrest in the presence of unreplicated DNA in somatic cells by phosphorylating Cdc25A and leading to its degradation. (vt.edu)
Chk1 plays a critical but not fully understood role in cell cycle remodeling and early embryonic development. (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)
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)
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)

Kinase inhibitors add another level of modulation. (wikipedia.org)
Kinase inhibitors are grouped into classes and are assigned not very descriptive acronyms. (wikipedia.org)
These include INKS for inhibitors of kinase, KIPS for kinase inhibitors and CKIPS for cyclin dependent kinases inhibitors. (wikipedia.org)
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)
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)
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)
This review examines how LSD1 modulates different cell behavior in TME and emphasizes the potential use of LSD1 inhibitors in combination with ICB therapy for future cancer research studies. (biomedcentral.com)
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)
The DNA in cancer cells can be damaged by a variety of treatments such as radiation, antimetabolites, alkylating agents, DNA topoisomerase inhibitors and platinum-based chemotherapy. (almacgroup.com)

Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. (wikipedia.org)
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)
After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. (jove.com)
When B levels drop, the cell exits mitosis and divides. (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)
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)
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)
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)
The term mitosis refers specifically to the process whereby the nucleus of the parent cell splits into two identical nuclei prior to cell division. (visionlearning.com)

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)
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)
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)
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)
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)
Cinobufotalin impedes Sw.71 cytotrophoblast cell line function via cell cycle arrest and apoptotic signaling. (tamu.edu)
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)
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)
While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. (biomedcentral.com)
ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. (princeton.edu)
All-trans retinoic acid (atRA) mediated growth inhibition results in the arrest of the cell cycle during the G1 phase in CAOV3 cells but not SKOV3 ovarian carcinoma cells. (temple.edu)

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)
We have found that a DNA replication checkpoint dependent on the ATM homolog MEC1 operates in wild-type cells during meiosis and can be invoked in response to inhibition of DNA synthesis. (ox.ac.uk)
Although cells that lack clb5 and clb6 are unable to activate the meiotic DNA replication checkpoint, they do possess an intact DNA damage checkpoint which can restrain chromosome segregation in the face of DNA damage. (ox.ac.uk)
We conclude that CLB5 and CLB6 are essential for premeiotic DNA replication and, consequently, for activation of a meiotic DNA replication checkpoint. (ox.ac.uk)

Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). (ox.ac.uk)

Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
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)
These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. (mdpi.com)
Growing knowledge regarding molecules that control the cell cycle and apoptosis is expected to contribute to the identification of new therapy targets. (iiarjournals.org)
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)
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)
Further, cell death effect of ST was associated with induction of apoptosis. (biomedcentral.com)

Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)

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)
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)
Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. (ibecbarcelona.eu)
β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
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)
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)
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 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)
ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. (elsevierpure.com)

Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair. (elsevierpure.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)
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)

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)

Scientists working in basic, translational, and clinical cancer metabolism research are invited to join the Academy in New York on April 17th to discuss the intersection between cell signaling and metabolism. (nyas.org)
Cancer Cell Metabolism: Unique Features Inform New Therapeutic Opportunities. (nyas.org)
Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. (biomedcentral.com)

In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
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)
5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
Dysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. (biomedcentral.com)
This innovative approach enhances the patient's immune system to target and eliminate tumor cells. (biomedcentral.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)
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)
The TNM (tumor-node-metastasis) staging system from the American Joint Committee for Cancer Staging and End Results Reporting is used for all lung carcinomas except small-cell lung cancer. (medscape.com)
In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. (medscape.com)

Cyclins are molecules that manage the timing of cell cycle events. (wikipedia.org)
Cyclin dependent kinases pair up with cyclins to become operational. (wikipedia.org)
Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. (wikipedia.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)
The B-type cyclins Clb5 and Clb6 are the primary activators of the S phase function of the budding yeast CDK Cdc28. (ox.ac.uk)
However, in mitotically growing cells this role can be fulfilled by the other B-type cyclins Clb1-Clb4. (ox.ac.uk)

current view for the silencing of the spindle assembly checkpoint. (fsu.edu)
It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. (umbc.edu)
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)
The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)

SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. (oncotarget.com)
In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (biomedcentral.com)
Our results show that overexpression of p16 in SKOV3 cells leads to growth inhibition following atRA treatment. (temple.edu)
Nevertheless, these results show that p16 plays a role in atRA mediated growth inhibition in ovarian carcinoma cells and that modulation of p16 expression can determine the growth response to atRA. (temple.edu)

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)

During the cell cycle, there are two main checkpoints that regulate entrance into S and M phases. (vt.edu)

Therefore, we conclude that DDK regulates a largely checkpoint-independent role of Claspin function. (caltech.edu)
Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. (umbc.edu)

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)

It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.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)

More than 90% of oral malignant neoplasms are squamous cell carcinomas (OSCC), which are among the ten most frequent malignancies in humans and this entity is the eighth leading cause of cancer-related death worldwide ( 1 ). (iiarjournals.org)
From experiments in the 1870s to research more than 100 years later, scientists have made fascinating discoveries about the complex series of events that allow the cells in plants and animals, including humans, to grow and sustain life. (visionlearning.com)

The Fanconi Anemia (FA) core complex localizes to chromatin during the S phase and in response to DNA damage. (kupferlab.org)

Rb is one of the most studied checkpoint molecules. (wikipedia.org)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
The TME consists of various cellular components, including immune cells, stromal cells, and extracellular matrix, along with soluble factors and signaling molecules. (biomedcentral.com)

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)

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)
At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. (oncotarget.com)
Two main etiologies of head and neck squamous cell carcinoma (HNSCC) are recognized that reveal distinct biological characteristics. (oncotarget.com)
The 13 homeobox genes were analyzed because previous studies done by our laboratory observed differences in expression of these homeobox genes when comparing atRA sensitive oral squamous carcinoma cells (SCC) to atRA resistant oral squamous cell carcinoma cells. (temple.edu)
Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) (see the image below), and large cell carcinoma. (medscape.com)
A cavitating right lower lobe squamous cell carcinoma. (medscape.com)
Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas. (medscape.com)
Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. (medscape.com)

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

Despite this defect, the mutant cells progress into the meiotic program and undergo lethal segregation of unreplicated DNA suggesting that they fail to activate a checkpoint that restrains meiotic M phase until DNA replication is complete. (ox.ac.uk)

The integrity of DNA replication control and checkpoint mechanisms is essential for preventing tumorigenesis. (caltech.edu)
[ 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)
Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.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)

During the last decade, the non-random spatial arrangement of the genome into the nucleus of eukaryotic cells, as emerged as a key regulator of genome functions and notably of the propagation of a stable genome. (cea.fr)

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)
Frequent inactivating mutations of the ATM gene have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL), B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma (MCL). (bmj.com)
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)

In its active state it is part of the checkpoint that blocks transition to anaphase. (wikipedia.org)

I am a senior lecturer in Cell Bilogy and a member of the plant biology group. (brookes.ac.uk)
Previous to this I completed my BSc in Cell and Human Biology here at Oxford Brookes University. (brookes.ac.uk)
For a century, the nucleus has been the focus of extensive investigations in cell biology. (brookes.ac.uk)

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)
As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)

Judith Balmaña, MD, PhD, of Vall d'Hebron University Hospital, discusses in Spanish the findings of a single-agent phase II trial on the antitumor activity of lurbinectedin in BRCA1/2-associated metas. (ascopost.com)
However, cancer cells exploit these checkpoints to evade immune surveillance and suppress antitumor immune responses. (biomedcentral.com)

Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. (bioone.org)
Epithelial cell divisions are coordinated with cell loss to preserve epithelial integrity. (ibecbarcelona.eu)

SRA737 is currently being investigated in two Phase 1/2 clinical trials primarily focused on patients with ovarian cancer: SRA737-01, a monotherapy study, and SRA737-02, a drug combination study evaluating SRA737 potentiated by low dose gemcitabine. (salesandmarketingnetwork.com)

In most cases, when a cyclin is degraded, the CDK is inactivated, signaling the end of a particular phase. (jove.com)
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)

Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. (fsu.edu)
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)

In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. (biomedcentral.com)

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

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

Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. (biomedcentral.com)

The Nek2 subfamily is one of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. (umbc.edu)
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)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
Within the core complex, both FANCA and FANCG are phosphorylated (P). In the presence of an intact core complex, FANCD2 is monoubiquitinated (Ub) on K561 and colocalizes in nuclear foci with BRCA1, where it carries out its roles in DNA repair and/or cell cycle control. (kupferlab.org)
Recent studies have examined the consequences of epigenetic marks and cell cycle control, which has led to more research regarding cell division cancer, emphasizing the fact that the cell division process requires accurate checkpoints to avoid genetic damage. (ptgcn.com)

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)

However, how epithelia adapt their rate of cell division to changes in cell number, for instance during homeostatic turnover or wounding, is not well understood. (ibecbarcelona.eu)
Orderly progressions of events in the cell division cycle are necessary to ensure the replication of DNA and cell division. (ox.ac.uk)
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)
Most of the cells that make up higher organisms, like vertebrate animals and flowering plants, reproduce via a process called cell division. (visionlearning.com)
In cell division, a cell makes a copy of its DNA and then separates itself into two identical cells - each with its own copy of DNA enveloped inside a nucleus. (visionlearning.com)
That's right, the hundreds of millions of cells that make up the bone and flesh of your body are products of thousands of generations of cell division that began when you were smaller than the period at the end of this sentence. (visionlearning.com)
In particular, he was interested in the process of cell division. (visionlearning.com)
The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication (replication) to produce two daughter cells. (ptgcn.com)

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)
In eukaryotic cells the genetic material is surrounded by a membrane system called the nuclear envelope (NE). (brookes.ac.uk)
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)
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)

CLB5 and CLB6 are required for premeiotic DNA replication and activation of the meiotic S/M checkpoint. (ox.ac.uk)
We report here that cells undergoing meiotic development also require Clb dependent CDK activity for DNA replication. (ox.ac.uk)

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 Nuclear Envelope is a hallmark of eukaryotic cells. (brookes.ac.uk)

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)

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)

Anatomy20

Organisms4

Diseases10

Chemicals and Drugs131

Analytical, Diagnostic and Therapeutic Techniques and Equipment16

Phenomena and Processes81

Disciplines and Occupations1

Information Science3

Health Care3

Proteins23

Inhibitor11

Phosphorylation8

CDKs8

Chk19

Inhibitors9

Mitosis11

Arrest21

Replication checkpoint5

Protein kinase1

Apoptosis7

Downstream1

Progression8

Activates2

Pathway3

Wee11

Metabolism3

Tumor10

Cyclins8

Spindle4

Inhibition5

Chk21

Regulate1

Regulates2

Proliferation2

Mitotic catastrophe2

Humans2

Chromatin1

Molecules3

Enzymes1

Squamous9

Genetics1

Lethal1

Mechanisms4

Regulator1

Gene3

Anaphase1

Biology3

Regulation2

Antitumor2

Epithelial cell2

Gemcitabine1

Signaling2

Chromosomes2

Immune checkpoint1

Mutation1

Degradation1

Developmental1

Control6

Damage-induced1

Division8

Genetic4

Meiotic2

Cdc71

Eukaryotic cells1

Differentiation1

Radiation1