Checkpoint mediated cell cycle arrest regulate cell cycle progression and checkpoints. Medical search. Frequent questions

The cell cycle is the process of accurate self-reproduction and proliferation of a cell. (intechopen.com)
Misregulation of the cell cycle may result in malignant cell proliferation, tumorigenesis or cell death. (intechopen.com)
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine assay, propidium iodide (PI) staining, annexin V-fluorescein isothiocyanate/PI staining, and transwell assay were employed to test the proliferation, apoptosis, migration ability, and invasiveness of COAD cells. (hindawi.com)
Upregulating the level of miR-323a-3p impaired the proliferation, migration, and invasion of COAD cells and promoted apoptosis, whereas supplementing NEK6 alleviated the damage of the proliferation, migration, and invasion of COAD cells caused by miR-323a-3p and inhibited miR-323a-3p-induced apoptosis. (hindawi.com)
These findings indicate that miR-323a-3p regulates the proliferation, migration, invasion, and apoptosis of COAD cells by targeting NEK6. (hindawi.com)
RAS proteins generated from mutant KRAS constitutively activate their downstream signaling pathways, such as those involved in the growth, proliferation, and survival of cancer cells [8]. (cellphysiolbiochem.com)
In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
An obvious requirement for the stringent control of cell cycle progression is the prevention of deregulated proliferation - loss of control may result in tumors and cancers. (janechin.net)
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)
Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
PD-1 expression by cancer cells blocks the proliferation of T-cells. (shu.edu)
P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)

Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. (medsci.org)
Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis, and which plays a critical role in tumor progression in various malignancies. (researchsquare.com)

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)
Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.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)

Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
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)
miRNAs expressed in a wide variety of human cancers can regulate posttranscriptional gene expression by binding to the 3′ untranslated region of the target mRNAs and act as oncogenes or tumor suppressors to regulate cell signaling pathways, affecting tumorigenesis and tumor progression [ 17 ]. (hindawi.com)
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)
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)
Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. (springer.com)
The suppressive effect of PD-1 on Skp2 expression was mediated by inhibition of both PI3K/Akt and Ras/MEK/Erk pathways and was only partially reversed by IL-2, which restored activation of MEK/Erk but not Akt. (shu.edu)

Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance. (babraham.ac.uk)
This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. (babraham.ac.uk)
Our findings demonstrate that PKM2 promotes tumor progression and galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. (researchsquare.com)
PD-1 inhibition (Figure 1) has quickly become a front-line therapy for non-small cell lung cancer and melanoma . (shu.edu)
This inhibition leads to a decrease in DNA synthesis during bacterial replication, resulting in cell growth inhibition and eventually cell lysis. (medindex.am)

ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.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)
p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
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)
p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)
Rad51-mediated replication of damaged templates relies on monoSUMOylated DDK kinase. (ifom.eu)

Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. (kegg.jp)
The mammalian cell cycle is stringently regulated and orderly process by which a cell reproduces. (janechin.net)
Orderly progression through the cell cycle involves passage through sequential checkpoints. (shu.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)
In COAD cells, NEK6 was highly expressed, whereas miR-323a-3p was expressed at low levels and negatively regulated NEK6. (hindawi.com)
STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. (medsci.org)

Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. (nature.com)
Factors mandating cellular consequence include cell surface-receptors, cytoplasmic proteins, and nuclear proteins. (janechin.net)
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)

To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. (cellphysiolbiochem.com)
Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
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)
Moreover, PD-1 and PD-L1 inhibitors are being tested in combination with other checkpoint inhibitors, targeted therapies, cancer vaccines, monoclonal antibodies, and other modalities. (shu.edu)

In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
Silencing of the transcription factor hCAS/CSE1L, which regulated PIG3 expression, led to decreased PIG3 transcription and concurrently decreased apoptosis ( 3 ). (ijbs.com)
Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.com)
We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. (cellphysiolbiochem.com)

In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
SUMO-Chain-Regulated Proteasomal Degradation Timing Exemplified in DNA Replication Initiation. (ifom.eu)

Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)

Plk1 is mainly expressed during the late G2 and M phase, where it regulates various stages of mitosis [ 2 , 7 ]. (oncotarget.com)
Stages of the cell cycle are G1 (Gap 1), S (Synthesis), G2, M (Mitosis), and G0 (quiescence), with mitosis as the shortest and most visually dramatic process of the cycle after which two daughter cells result, Figure 1-1. (janechin.net)

PIG3 is highly homologous to NADPH oxidoreductase TED2 in plants and zeta-Crystalline in mammalian cells, and is considered as a proapoptosis marker. (ijbs.com)
The mammalian cell cycle typically completes in 24 hours, where dramatic changes occur in cellular metabolism and cytoskeletal physiology. (janechin.net)
The mammalian cell is furnished with receptors linked to interactive series of cytoplasmic networks for controlling cellular processes. (janechin.net)

Modern approaches to treating cancer take advantage of critical biochemical differences between cancer cells and normal cells - from radiation therapy to chemotherapy to experimental gene therapy. (janechin.net)
Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
Subsequently, T cells receiving PD-1 signals displayed impaired Cdk2 activation and failed to phosphorylate two critical Cdk2 substrates, the retinoblastoma gene product (Rb) and the TGFβ-specific transcription factor Smad3 , leading to suppression of E2F target genes but enhanced Smad3 transactivation (Figure 3). (shu.edu)
Activated complexes accumulate in the nucleus where they cooperate with DNA-binding cofactors to regulate target gene transcription. (shu.edu)

SMC complexes are guarded by the SUMO protease Ulp2 against SUMO-chain-mediated turnover. (ifom.eu)

However, pimecrolimus mode of action is cell-selective and does not affect Langerhans' cells/dendritic cells and primary fibroblasts. (medindex.am)

The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
Each stage of the cell cycle is profiled by distinct protein complexes and phosphorylation events. (janechin.net)
Cells have a protein on their surface called PD-1 (in orange above). (shu.edu)

The Warburg hypothesis was based on the metabolic differences between cancer cells and normal cells, and proposed that increased glycolysis by transformed cells conferred a bio-energetic advantage for survival over normal counterparts under anoxic conditions (Anghileri, 1983). (janechin.net)

5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)

Comparative biochemical studies of rapamycin and wortmannin on transforming growth factor-beta 1 (TGF-beta1)-mediated G(1)-S cell cycle progression in C3H-10T1/2 embryonic fibroblasts. (janechin.net)
In embryonic stem cells, SMAD2/3-TIF1γ recognizes specific chromatin marks, promoting access of SMAD2/3-SMAD4 to otherwise repressed targets. (shu.edu)

Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)

CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)

Anti-PD-1 antibodies (dark green) or anti-PD-L1 antibodies (light green) can prevent the tumor cell from binding PD-1 and thus allow T cells to remain active. (shu.edu)

Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)

This observation prompted us to characterise the cell-autonomous cytotoxic and anti-proliferative profile of gomesin in DFTD cells and in comparison, to non-transformed (healthy) Tasmanian devil fibroblasts (FIBS). (nature.com)

To test the hypothesis that escape from G1 arrest in drug promotes amplification, we exploited the combination of palbociclib and selumetinib. (babraham.ac.uk)
However, how metabolism reprogramming promotes tumor progression and immune escape remains unclear. (researchsquare.com)
However, how PKM2 promotes tumor progression and its mechanism remain obscure. (researchsquare.com)

Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. (springer.com)

These factors couple extracellular signals to intracellular processes to determine cell cycle progression. (janechin.net)
Dysregulation of processes driven by these factors is a severe liability to the cell and therefore represents potential areas for therapeutic intervention. (janechin.net)

Preincubation with an autophagy inhibitor accelerated cell death. (cellphysiolbiochem.com)
Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. (cellphysiolbiochem.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)
In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
The DNA double-strand break (DSB) is considered to be the most severe type of DNA damage induced by ionizing radiation, and this form of DNA damage must be repaired immediately to prevent cell death. (ijbs.com)

Lactate production and the expression of galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. (researchsquare.com)

Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
Transitional checkpoints are therefore crucial for a successful completion of the cell cycle. (janechin.net)

When cells proliferate in the absence of appropriate driving signals, cancer is the undesirable consequence. (janechin.net)
Extracellular signals direct the cell-cycle 'engine. (janechin.net)
The Restriction point is also known as a checkpoint, where 'the cell is arrested at a particular phase of the cycle due to a lack of appropriate signals' (Hartwell and Weinert, 1989). (janechin.net)
Restriction points receive signals from central- and peripheral cellular networks to determine subsequent cell fate. (janechin.net)
As a consequence, the synthesis and release of Th1- (T helper 1) and Th2- (T helper 2) type cytokines, and other inflammatory mediators from T-cells and mast cells are blocked and the expression of signals essential for the activation of inflammatory T-lymphocytes is inhibited. (medindex.am)

The increased calcium influx into the pancreatic beta cells induces insulin secretion, thereby lowering blood glucose levels. (medindex.am)

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)

As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
Encouraging progress in understanding cell cycle regulation occurred over the past five years. (janechin.net)
Such regulation ensures faithful reproduction of DNA for subsequent distribution to daughter cells. (janechin.net)

Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
Plk3 is expressed throughout the cell cycle and involved in cellular response to DNA damage [ 9 ]. (oncotarget.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)
J-H Lee et al extensively investigated the participation of PIG3 in DNA damage checkpoints after UV irradiation or after treatment using the radiomimetic drug neocarzinostatin (NCS) ( 8 ). (ijbs.com)

Therefore, understanding biochemical dynamics of cell cycle progression may lead to target-specific therapy with improved side effect profiles. (janechin.net)
Using Cell Cycle-Restricted Alleles to Study the Chromatin Dynamics and Functions of the Structural Maintenance of Chromosomes (SMC) Complexes In Vivo. (ifom.eu)

Accumulation of p27 in the nucleus, therefore, blocks cell cycle progression of T-lymphocytes that are being induced to act against cancer antigens. (shu.edu)

Repaglinide blocks ATP-dependent potassium channels in pancreatic beta cells, thereby causing depolarization of the cell membrane and subsequent opening of calcium channels. (medindex.am)

In this study, we aimed to investigate the effects of miRNAs targeting NEK6 in COAD cells. (hindawi.com)

To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. (cellphysiolbiochem.com)
CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. (cellphysiolbiochem.com)
CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities. (cellphysiolbiochem.com)

Signaling specificity is conferred by receptors and mediated through associated-kinases. (janechin.net)
TGF-β ligands bind type I and type II receptors at the cell surface. (shu.edu)

The activity of NEK6 is enhanced in several cancer cells, including colon adenocarcinoma (COAD) cells. (hindawi.com)
Also, PIG3 has been reported to have oxidoreductase enzymatic activity ( 4 ), this provides direct evidence of PIG3's participation in the generation of ROS in cells. (ijbs.com)

Re-expression of PIG3 effectively rescued the depression of DNA-PKcs in PIG3-depleted cells. (ijbs.com)
Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)

We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell. (mdpi.com)

When PD-1 binds to PD-L1 (yellow) on another cell, the T cell becomes deactivated. (shu.edu)
Pimecrolimus binds to the receptor macrophilin-12 (FKBP-12) forming a complex that blocks the calcium-dependent signal transduction cascade mediated by calcineurin. (medindex.am)

Anatomy23

Organisms10

Diseases9

Chemicals and Drugs117

Analytical, Diagnostic and Therapeutic Techniques and Equipment19

Phenomena and Processes84

Disciplines and Occupations1

Information Science3

Health Care3

Proliferation12

Role in tumor progression2

Mitotic5

Pathways8

Inhibition7

Intra-S-phase2

Kinase7

Orderly3

Negatively3

Proteins3

Inhibitors5

Apoptosis4

Replication initiation3

Tumour cells1

Mitosis2

Mammalian3

Gene4

Turnover1

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Protein4

Metabolic1

Glycolysis1

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Phases1

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Melanoma1

Anti-proliferative1

Promotes3

Radiation therapy1

Processes2

Inhibitor2

Ionizing radiation3

Knockdown1

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Signals5

Induces1

Sufficient1

Regulation3

Response2

Damage2

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Nucleus1

Subsequent1

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Receptors2

Activity2

Expression2

Cancer cell1

Binds2