Phosphorylation damage checkpoint pathway. Medical search. Frequent questions

Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
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)
Change in localisation depends on the checkpoint kinases Tel1ATM and Mec1ATR and has a positive effect on spontaneous recombination. (cea.fr)
12] "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. (tcdb.org)
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)
In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
The Chk1 kinase and its main upstream activator kinase, ATR, are essential checkpoint effectors in response to a wide variety of genotoxic tensions, and inhibit source firing by focusing on the replication kinases, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) [21], while Chk2 and its main upstream activator ATM are primarily associated with the cellular response to double-strand DNA breaks [22]. (ampkpathway.com)
Cell-cycle kinases DDK and CDK are needed upstream for the activation from the MCM complicated and several PGE1 ic50 research have defined the checkpoint-dependent phosphorylation of MCM proteins [24C27], although certain requirements or results for these adjustments for activity or stability from the helicase still stay unclear. (ampkpathway.com)
FANCD2 is a phosphorylation target of kinases ATM and perhaps ATR, a phosphorylation that is necessary to maintain the S-phase checkpoint. (kupferlab.org)

Simultaneous measurements of glycolysis and oxidative phosphorylation in live cells revealed that OB differentiation decreased the oxygen consumption rate, which indicates reduced ATP production and mitochondrial respiration. (nih.gov)
Converting glucose to lactate, rather than metabolizing it through oxidative phosphorylation in the mitochondria, is far less efficient as less ATP is generated per unit of glucose metabolized. (sigmaaldrich.com)
Mitochondria are the energy producing organelles in eukaryotic cell providing ATP through oxidative phosphorylation (OXPHOS). (hindawi.com)
Dr. Otto Warburg first described, more than 80 years ago, that a fundamental biochemical difference between tumor cells and their normal counterparts was that tumor cells rely on aerobic glycolysis for ATP generation, unlike most normal differentiated cells of the body, which use mitochondrial oxidative phosphorylation. (aacrjournals.org)
Transcriptomics analyses showed pathways related to TCR signaling, cytotoxicity and oxidative phosphorylation were significantly enriched in Tet lo found in both regressing and progressing tumors compared with Tet hi , whereas genes related to DNA damage, apoptosis and autophagy were downregulated. (bmj.com)
GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. (medsci.org)

Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. (nih.gov)
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)
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)
Chk1 is a checkpoint kinase activated during genotoxic stress. (reactome.org)
Mutational analysis indicates that modification of both sites is essential for maximal kinase activity, while phosphorylation of only a single site causes only weak activation of Chk1. (reactome.org)
Analogous to the Chk1 kinase existing downstream of ATR, the Chk2 checkpoint kinase is modified and activated by ATM. (reactome.org)
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. (reactome.org)
In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
LKB1 is a serine/threonine kinase mutated in Peutz-Jeghers syndrome (PJS), implicated in many cellular processes including energy metabolism, cell polarization and cell cycle arrest and has also been shown to play an essential role as a tumor suppressor gene by negatively regulating the mTOR pathway. (scirp.org)
Another important pathway is the AMP-activated protein kinase (AMPK) pathway. (sigmaaldrich.com)
This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.com)
Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)

Whereas the different DNA repair pathways and the proteins they involve are know pretty well described, how they are regulated relative to each other in time and space remains to be deciphered. (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)
11] "Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. (tcdb.org)
hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)
In order to investigate the part of MCM PGE1 ic50 proteins in the cellular response to DNA damage, we used shRNA focusing on MCM2 or MCM3 to determine the impact of the reduction in MCM complex within the DDR. (ampkpathway.com)
The alteration of MCM proteins induced a change in the activation of important factors of the DDR in response to Etoposide treatment, including influencing the phosphorylation of -H2AX, CHK1 and CHK2 following Etoposide-induced DNA damage without inducing changes in cell viability, but resulting in a small decrease in DNA replication. (ampkpathway.com)
Results Reducing MCM2 or MCM3 proteins does not impact cell growth Our previous results showed an involvement of MCM proteins in the DNA damage response through its co-localization with -H2AX foci, and through connection with chromatin redesigning proteins in response to DNA damage induced from the topoisomerase II inhibitor Etoposide [28]. (ampkpathway.com)
To investigate the part of the PGE1 ic50 MCM proteins in regulating cell growth as well as investigate the signaling of DNA damage, we used shRNAs delivered Rabbit polyclonal to ACSS2 through lentiviruses focusing on MCM2 (shMCM2) or MCM3 (shMCM3) in the U2OS cell line, as well as a non-silencing control (shControl). (ampkpathway.com)
Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
The mitochondria have their own chaperones and proteolytic enzymes that remove damaged or unfolded proteins [ 18 - 20 ]. (hindawi.com)
Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. (wustl.edu)
J-H Lee et al also have provided the first evidence showing that PIG3 is closely associated with the induction and maintenance of the phosphorylation of H2AX and some other DDR proteins after DNA damage induced by NCS ( 8 ). (ijbs.com)
These proteins act primarily at the G1 checkpoint. (byui.edu)

Chk1 is regulated by ATR through phosphorylation, forming the ATR-Chk1 pathway. (wikipedia.org)

The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
The checkpoint clamp Rad9-Hus1-Rad1 (9-1-1) is loaded by the Rad17-RFC complex onto chromatin after DNA damage and plays a key role in the ATR-dependent checkpoint activation. (elsevierpure.com)
The Fanconi Anemia (FA) core complex localizes to chromatin during the S phase and in response to DNA damage. (kupferlab.org)
We discuss what factors determine the sub pathway choice including etiology of the DSB, chromatin structure at the break site, processing of the DSBs and the mechanisms regulating the sub-pathway choice. (springeropen.com)

Upregulation of numerous IFN-γ-inducible chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the complex immune response to MIBC. (sciencegate.app)
this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
The suppression of this repair pathway increases the abundance of micronuclei that trigger the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and subsequent interferon-ß (IFN-ß) production. (bvsalud.org)
These receptors function as ligand-dependent transcription factors [2] - [4] , acting either through the transcriptional regulation of genes (genomic pathway) or through membrane and cytoplasmic signaling cascades (non-genomic pathway). (scirp.org)
This checkpoint control is critical to avoid genomic instability, and mutations in PGE1 ic50 checkpoint genes are often associated with malignancy [19,20]. (ampkpathway.com)

The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)
Triphala-induced apoptosis was linked with phosphorylation of p53 at Ser-15 and ERK at Thr-202/Tyr-204 in Capan-2 cells. (biomedcentral.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)
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)
EPCs from human umbilical cord and adult peripheral blood activate different mechanisms upon high-dose x-ray radiation treatment: CB-EPCs undergo p53 stabilization, Bax-dependent apoptosis and p21-dependent G 1 and G 2 /M cell cycle checkpoints, while PB-EPCs undergo only radiation-induced senescence [ 13 ], indicating unique gene expression patterns in EPCs of different sources. (biomedcentral.com)
Upon publicity to a genotoxin cells undergo apoptosis, development arrest, and cell cycle checkpoint arrest according to the extent on the damage. (cetp-signal.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)
2011 These results suggested that caffeine induced WYE-125132 apoptosis in tumors by inhibiting the ATR/Chk1 pathway and by advertising lethal mitosis. (technologybooksindustrialprojectreports.com)
Silibinin considerably reduced the development of oral cancer cells by inducing apoptosis, G 0 /G 1 arrest, ROS generation, and activation of the JNK/c-Jun pathway. (jcancer.org)

Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. (wikipedia.org)
Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)

Intriguingly, activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation. (bvsalud.org)
Activation of Chk1 occurs following phosphorylation of two sites (serine 317 and serine 345). (reactome.org)
Further analyses showed that phosphorylation at both serine residues occurs in vivo and is required for the efficient interaction with TopBP1 in vitro. (elsevierpure.com)
These data illustrate the powerful legislation of checkpoint function recommending that phosphorylation of Chk1 on Serine 317 is WYE-125132 normally controlled by p53 position which p53 may become a molecular on/off change for phosphorylation here. (technologybooksindustrialprojectreports.com)

Studies on Chk1 deficient chicken lymphoma cells have shown increased levels of genomic instability and failure to arrest during the spindle checkpoint phase in mitosis. (wikipedia.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)
In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)

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)
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)
One particular with the intracellular signal transduction pathways that drives tumorigenesis and cancer progression is definitely the Ras Raf Mek Erk pathway. (cetp-signal.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)

AMPK is often considered a metabolic checkpoint as it can control cell proliferation when activated under energetic stress, and activation of AMKP results in the inhibition of mTOR activity. (sigmaaldrich.com)
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 recent examine showed that maintenance of protein tyrosine phosphorylation by PTP inhibition was connected with increased cell proliferation, clonogenic survival, and mutagenesis following just one Cr publicity in human lung fibroblasts. (cetp-signal.com)
Notably, PTP inhibition enhanced Cr induced forward Cyclovirobuxine D mutations at the HPRT locus in two mammalian cell lines, which was coincident with enhanced clonogenic survival, suggesting regulators of tyrosine phosphorylation might figure out cell survival death as an initial event just after Cr insult. (cetp-signal.com)

harm affected the phosphorylation of -H2AX, CHK2 and CHK1 without affecting cell viability. (ampkpathway.com)
Whereas Chk1 and Chk2 have been reported to be involved in unique signaling pathways originally, there is certainly installation proof for a thorough crosstalk between ATR-Chk1 and ATM-Chk2 controlled checkpoint replies [23]. (ampkpathway.com)

RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle. (wikipedia.org)
We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. (nih.gov)
cells in recognizing damaged or broken DNA strands. (diff.org)
many of the body's cells from correctly repairing damaged DNA. (diff.org)
Estrogens stimulate the proliferation and the differentiation of breast epithelial cells through the activation of downstream mitogenic signaling pathways, namely via the estrogen receptors ERα and ERβ. (scirp.org)
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)
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)
Abstract Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. (techscience.com)
Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. (techscience.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)
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)
However continued UVB exposure increases the rate of recurrence of p53 mutant clones in pores and skin which can lead to the selective loss of the G1 checkpoint pathway therefore sensitizing the cells to UV-damage and enhancing carcinogenesis. (technologybooksindustrialprojectreports.com)
Recent mechanistic studies from our laboratory showed that caffeine inhibited the ATR/Chk1 pathway improved the number of apoptotic cells and reduced tumor formation in UVB-exposed epidermis MTRF1 (Huang et al. (technologybooksindustrialprojectreports.com)
Western blotting revealed that silibinin downregulated SOD1 and SOD2 and triggered the JNK/c-Jun pathway in oral cancer cells. (jcancer.org)

Additional protein interactions are involved to induce maximal phosphorylation of Chk1. (wikipedia.org)
Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)

10] "Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae. (tcdb.org)
Both homologous recombination, in which the ends of the broken DNA seek out intact templates with the same sequence, and nonhomologous end-joining pathways are found in Saccharomyces as they are in humans. (brandeis.edu)

ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. (nih.gov)
The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)

These studies suggest Chk1 depletion can lead to defects in the spindle checkpoint resulting in mitotic abnormalities. (wikipedia.org)
The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)

2010 UVB-induced DNA damage activates the ATR signaling pathway leading to elevated p53 and phospho-Chk1 (Ser317) and cell cycle arrest therefore allowing time for DNA restoration. (technologybooksindustrialprojectreports.com)

Therefore, a metabolic shift from mitochondrial respiration to the glycolytic pathway occurs during OB differentiation. (nih.gov)
Moreover, nonreversible mitochondrial damage targets the organelle to a specific autophagic removal, namely, mitophagy. (hindawi.com)

Inhibitors of the glycolytic pathway, such as dichloroacetic acid (DCA) and 2-deoxy-d-glucose (2DG) are now being used in clinical studies as potential anticancer agents. (sigmaaldrich.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)

This "in vivo biochemistry" approach has enabled us to demonstrate that there are in fact several independent, competing pathways of homologous recombination, each with its own genetic requirements. (brandeis.edu)
The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is considered to be error-prone, intrinsically mutagenic quick fix remedy to seal together the broken DNA ends and restart replication. (springeropen.com)

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)

This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. (elsevierpure.com)
Using this system, we showed that ATRIP was crucial for DNA damage-induced FANCD2 monoubiquitination and FANCI phosphorylation. (elsevierpure.com)
Mechanistic investigations revealed that the RPA region but not the TopBP1 region of ATRIP was required for FANCD2 monoubiquitination, whereas Chk1 phosphorylation relied upon both domains. (elsevierpure.com)

Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)

These ssDNA structures attract ATR and eventually activates the checkpoint pathway. (wikipedia.org)

However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. (nih.gov)

The PI3K pathway is considered to be a major determinant of the glycolytic phenotype through AKT1 and mTOR signaling, and subsequent downstream Hypoxy Inducible Factor 1 (HIF-1) transcription factor activation. (sigmaaldrich.com)

Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)
Dr. Maity obtained his Ph.D. in Cellular and Molecular Biology from the Life Science and Biotechnology department at Jadavpur University, India in 2017, where he studied the DNA damage repair protein WRN and autophagy. (nih.gov)
Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
The proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)

DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (wikipedia.org)

Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway. (nih.gov)

DNA damage, from cellular metabolism or exogenous sources, and unscheduled oncogene expression both lead to replicative stress and represent major sources of genetic instability. (oncotarget.com)

Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)

Moreover, we observed that hMYH was essential for the accumulation of hTopBP1 on damaged DNA, where hTopBP1 interacts with hRad9, a component of the Rad9-Hus1-Rad1 complex. (biomedcentral.com)
The Ras Raf Mek Erk pathway interacts with other mitogenic pathways to find out cell fate after extracellular stimuli. (cetp-signal.com)

Signaling pathways that regulate cell survival and proliferation are altered within the operation of carcinogenesis. (cetp-signal.com)

Studies from a number of laboratories in the past decade have revealed that the central pathways deregulated in cancer often serve to coordinately regulate both classic oncogenic signaling pathways controlling cell proliferation and cell survival with pathways controlling cell metabolism. (aacrjournals.org)

DNA can be damaged by agents such as toxic chemicals or radiation. (diff.org)
hypersensitive to radiation and do not respond normally to DNA damage. (diff.org)
However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. (techscience.com)
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)

During RT, alterations in signaling pathways result in changes in the local immune microenvironment. (nature.com)
Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. (wustl.edu)

Chk 1 activation occurs primarily through the phosphorylation of the conserved sites, Ser-317, Ser-345 and less often at Ser-366. (wikipedia.org)

Although phosphorylation of H2A represents a major histone modification that functions in DNA repair, a growing body of literature has implicated additional histone modifications. (cea.fr)

In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
Importantly, activation of TAK1 by monophosphoryl lipid A, a TLR4 agonist, boosts cGAMP-induced antitumor immunity dependent on STING phosphorylation in a mouse allograft tumor model. (bvsalud.org)
Taken together, TAK1 was identified as a checkpoint for STING activation by promoting its trafficking, providing a basis for combinatory tumor immunotherapy and intervention in STING-related diseases. (bvsalud.org)
We discover that Mtb promotes lipid droplets by inhibiting DNA repair responses, resulting in the activation of the type-I IFN pathway and scavenger receptor-A1 (SR-A1)-mediated lipid droplet formation. (bvsalud.org)
UreC-mediated activation of the IFN-ß pathway upregulates the expression of SR-A1 to form lipid droplets that facilitate Mtb replication. (bvsalud.org)
Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)

In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, egg production, embryo development, cellular responses to HIV infection and somatic cell viability. (wikipedia.org)
HR comprises different pathways: gene conversion (GC) that accurately repair the lesion by copying the homologous sequence, single strand annealing (SSA) or break induced replication (BIR) that can both lead to loss of genetic information. (cea.fr)
The p53-inducible gene 3 (PIG3) recently has been reported to be a new player in DNA damage signaling and response, but the crucial mechanism remains unclear. (ijbs.com)

Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy. (wustl.edu)

Our observations suggest that CK2 plays a crucial role in the ATR-dependent checkpoint pathway through its ability to phosphorylate Ser-341 and Ser-387 of the Rad9 subunit of the 9-1-1 complex. (elsevierpure.com)

Previously, it was thought the Warburg effect was a consequence of damage to the mitochondria or an adaptation to hypoxic conditions during the early avascular phase of tumor development. (sigmaaldrich.com)

Estrogen signaling pathways have been identified as efficient targets of breast cancer therapy, given their key role in promoting breast tumor growth. (scirp.org)

This delay allows time for DNA to repair or cell death to occur if DNA damage is irreversible. (wikipedia.org)
DNA double strand break repair (DSBR) pathways are generally classified based on whether sequence homology is used to join the broken DNA ends. (springeropen.com)
Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)
EPCs are currently being tested in different clinical settings including repair of damaged microcirculation, regeneration of ischemic tissues, and bioengineering of vascular grafts ( http://www.clinicaltrials.gov/ ). (biomedcentral.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)

The emergence of these findings, suggesting a direct control of cellular metabolism by tumorigenic pathways, has helped fuel explosive growth in this area of cancer research. (aacrjournals.org)

UV irradiation represents a major challenge to genomic integrity throughout the evolution of terrestrial organisms, resulting in the development of specific mechanisms that govern the cellular response to UV-induced DNA damage. (rupress.org)
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)

Anatomy22

Organisms10

Diseases4

Chemicals and Drugs132

Analytical, Diagnostic and Therapeutic Techniques and Equipment16

Phenomena and Processes78

Information Science3

Health Care3

Kinases10

Oxidative6

Kinase17

Proteins14

Forming the ATR-Chk1 pathway1

Chromatin4

Genes5

Apoptosis9

Genome2

Serine4

Mitosis3

Progression4

Inhibition4

Chk22

Cells15

Induce2

Saccharomyces2

Ataxia-telangiectasia2

Mitotic2

Cell cycle arrest1

Mitochondrial2

Glycolytic pathway1

Metabolic pathways1

Homologous recombination2

Inhibitors1

FANCD23

Recombination1

Activates1

Arrest1

Downstream1

Molecular4

Induces1

Additionally1

Instability1

Important roles in DNA replication1

Interacts2

Regulate cell1

Survival1

Radiation5

Immune2

Occurs1

Histone1

Activation6

Gene3

Annotation1

RAD91

Mitochondria1

Tumor growth1

Repair4

Targets1

Cellular metabolism1

Mechanisms2