• Correspondingly, most cancer signaling pathways seem to converge on one or more TFs, termed "master regulators" (MRs) [ 4 ], which direct tumor development, progression, and metastasis through hierarchical control of gene expression patterns. (aging-us.com)
  • Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
  • Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. (icr.ac.uk)
  • The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. (nih.gov)
  • Phosphatase 1 Nuclear Targeting Subunit (PNUTS) Regulates Aurora Kinases and Mitotic Progression. (nih.gov)
  • Taken together, the current results demonstrate that MAPK1 promotes myeloid cell proliferation and differentiation simultaneously by cell cycle progression while suppresing apoptosis. (prinsesmaximacentrum.nl)
  • 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)
  • 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)
  • However, whether PKM2 can promote head and neck squamous cell carcinoma (HNSCC) progression and immunosuppression remains unknown. (researchsquare.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)
  • Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)
  • In the present study, we investigated the relationship of gene expression profiles with malignant progression of human glioma. (biomedcentral.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)
  • Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. (gsea-msigdb.org)
  • PD-1 blocks cell cycle progression in the G 1 phase. (shu.edu)
  • Thus, PD-1 targets Ras and PI3K/Akt signaling to inhibit transcription of Skp2 and to activate Smad3 as an integral component of a pathway that regulates blockade of cell cycle progression in T lymphocytes. (shu.edu)
  • 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)
  • Orderly progression through the cell cycle involves passage through sequential checkpoints. (shu.edu)
  • In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
  • Here, we collected blood samples from a single, naturally infected Holstein cow at three disease progression stages (Stage I: polyclonal stage, Stage II: polyclonal toward oligoclonal stage, Stage III: oligoclonal stage) and successfully visualized the kinetics of clonal expansion of cells carrying BLV integration sites using our BLV proviral DNA-capture sequencing method. (biomedcentral.com)
  • Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. (microbiologyresearch.org)
  • Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
  • We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
  • RNR contains two subunits: ribonucleotide reductase subunit M1 (RRM1) and M2 (RRM2) [ 16 ]. (nature.com)
  • Liu C, Powell KA, Mundt K, Wu L, Carr AM, Caspari T., 2003 , Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms Genes Dev. (bangor.ac.uk)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
  • The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key component of the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSB) repair and is required for cellular resistance to ionizing radiation (IR) ( 1 , 2 ). (amegroups.org)
  • Protein Phosphatase 2A (PP2A) is a widely expressed family of protein phosphatases made of a core dimer, composed of a catalytic (C) subunit and a structural (A) subunit, in association with a third variable regulatory (B) subunit. (ac.be)
  • The regulation of PP2A is mainly accomplished by the identity of the regulatory B-type subunit, which determines substrate specificity, subcellular localization and catalytic activity of the PP2A holoenzyme. (ac.be)
  • The best evidence for a shelterin-specific role in telomerase regulation comes from analysis of TPP1, which interacts with the telomerase catalytic subunit through the N-terminal OB-fold domain of TPP1 [ 15 - 18 ]. (prolekarniky.cz)
  • Ku70/80 forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK [7]. (termedia.pl)
  • The amino-terminal non-catalytic region of Salmonella typhimurium SigD affects actin organization in yeast and mammalian cells. (microbiologyresearch.org)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • 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)
  • Inhibition of DNA-PKcs activity via a small interfering RNA or a kinase inhibitor results in mitosis delay, abnormal spindle formation, and chromosome misalignment. (amegroups.org)
  • 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)
  • 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)
  • Probably the most abundant viral transcripts in latency will be the U RNAs, which are selelck kinase inhibitor transcribed by DNA poly merase III and reach copy numbers of as much as two 104 copies per cell even though they aren't vital for transformation. (sodiumchannel-signal.com)
  • Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.com)
  • Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‑protein interaction network and survival analyses. (cancerindex.org)
  • Therefore, the aim of the present study was to investigate the gene expression patterns following siRNA‑mediated suppression of RUNX1‑RUNX1T1 and MAPK1 in Kasumi‑1 and SKNO‑1 cells and to determine the differentially expressed genes in enriched biological pathways. (prinsesmaximacentrum.nl)
  • 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)
  • Mayor Salomon is out that Freiburgers build more than the skeleton or mitotic T-cell. (evakoch.com)
  • The abnormally high number of centrosomes found in many human tumor cells can lead directly to aneuploidy and genomic instability through the formation of multipolar mitotic spindles. (umassmed.edu)
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • Mahyous Saeyd Salah Adam, Ewert-Krzemieniewska Katarzyna, Liu Boyin, Caspari Thomas, 2014 , Hyperactive Cdc2 kinase interferes with the response to broken replication forks by trapping S.pombe Crb2 in its mitotic T215 phosphorylated state . (bangor.ac.uk)
  • 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)
  • It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. (biomedcentral.com)
  • Changes in cortical neurones included alterations in insulin and other signalling pathways, cell cycle, cellular senescence, inflammatory mediators, and components of the mitochondrial respiratory electron transport chain. (biomedcentral.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)
  • also, the 5' download volatility trading of the cytoplasm is involved actually by cationic end-product by the RNase proximity water cell, which has a direct RNA( RNA H1 in pathways) and at least 10 Fructose-6-phosphate nucleus( activated in Jarrous 2002, Xiao et al. (evakoch.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)
  • 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)
  • Functional analysis of these genes indicated that several promising pathways were identified, including the DNA repair related Fanconi Anemia pathway and HIF-1 signaling pathway. (oncotarget.com)
  • Generally, the ablation of two genes located in parallel pathways (leading to cell survival or a common essential product) is one of the important patterns causing synthetic lethality (SL) [ 2 ]. (oncotarget.com)
  • Within the underlying theme of our research, we explore T cell responses from two complementary angles: the molecular pathways intrinsic to T cells, and the pathways that act in dendritic cells to cross-regulate T cell responses. (stjude.org)
  • For dendritic cell-mediated extrinsic control of T cell differentiation, we focus on metabolic and inflammatory pathways (see Du Nature 2018). (stjude.org)
  • Lipids, amino acids, and nucleotides necessary for the biosynthesis of the daughter cells are mostly provided by intermediate metabolites of these pathways. (hindawi.com)
  • To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)
  • Our data uncover novel details about the differential contribution of B2 vs four integrins within the composite phenotype of chronic asthma development and contribute towards the understanding of mechanisms by which different cell subsets and molecular pathways participate in the pathophysiology and histopathology of chronic asthma. (sodiumchannel-signal.com)
  • 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)
  • Hexokinase (HK), phosphofructokinase-1 (PFK-1) and pyruvate kinase (PK) are the three key enzymes in the glycolysis pathway. (researchsquare.com)
  • Currently, there are 49 genes in SZGR 2.0 (with evidence in schizophrenia) that are present at this pathway. (uth.edu)
  • DNA-PKcs and the NHEJ pathway are also essential for V(D)J recombination during T and B cell lymphocyte development. (amegroups.org)
  • Impaired insulin signalling was shared by neurovascular unit cells with, additionally, apoptotic pathway changes in astrocytes and dysregulation of advanced glycation end-product signalling in endothelial cells. (biomedcentral.com)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.com)
  • The nudF gene of the filamentous fungus Aspergillus nidulans acts in the cytoplasmic dynein /dynactin pathway and is required for distribution of nuclei. (xenbase.org)
  • 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)
  • Genes that suppress carcinogenesis have been classified as gatekeepers that regulate cellular proliferation and cell death and as caretakers that are primarily encode DNA repair proteins required for the maintenance of genome integrity ( 15 ). (amegroups.org)
  • The expression and cellular localisation of proteins encoded by selected candidate genes were confirmed by immunohistochemistry. (biomedcentral.com)
  • 4 While proteins can be phosphorylated on nine amino acids, serine, threonine and tyrosine phosphorylation are by far the most predominant in eukaryotic cells. (ac.be)
  • 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)
  • 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)
  • 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)
  • This download is the types and cells led from a human assembly target content soccer methylated alongside the set of two interaction localizing enzyme proteins in New Zealand. (evakoch.com)
  • My work provides mechanistic clues for cyclinspecific events during the cell cycle, demonstrates the usefulness of synthetic strategies in problem solving and also possibly resolves long-standing uncertainties regarding functions of some cell cycle proteins. (umassmed.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)
  • Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
  • In the case of the infectious cycle, viruses reach target lymphocytes by cell-to-cell transfer and establish by entry of viral single-stranded RNA, reverse transcription of the viral RNA, integration as a provirus into the host genome, expression of viral proteins, and budding of new virions. (biomedcentral.com)
  • Further, we review the corresponding genes and the proteins encoded by these genes, their possible role in the developing brain and reported mutations of these genes. (biomedcentral.com)
  • This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
  • In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. (ac.be)
  • But advances in the understanding of protein phosphatases make now clear that these enzymes are precisely regulated and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. (ac.be)
  • cooling work PI3K and changes car, the HSV-1 activator serves needed by the MRN blood( MRE11A: RAD50: NBN) and RBBP8( CtIP) considered with BRCA1: BARD1, and coupled by EXO1 or DNA2 in subunit with DNA enzymes BLM, WRN and BRIP1( BACH1)( Sartori et al. (familie-vos.de)
  • Identification of master regulator (MR) genes offers a relatively rapid and efficient way to characterize disease-specific molecular programs. (aging-us.com)
  • Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). (icr.ac.uk)
  • BeadChip microarray and gene ontology analysis revealed that RUNX1‑RUNX1T1 and MAPK1 suppression reduced the proliferation rate of the t(8;21) cells with deregulated expression of several classical positive regulator genes that are otherwise known to enhance cell proliferation. (prinsesmaximacentrum.nl)
  • Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
  • The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)
  • For example, a major regulator of metabolism is phosphoinositol 3 kinase (PI3K). (hindawi.com)
  • Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. (biomedcentral.com)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. (biomedcentral.com)
  • It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
  • Further, cell death effect of ST was associated with induction of apoptosis. (biomedcentral.com)
  • The p53-inducible gene 3 (PIG3) was originally indentified by Polyak et al in the analysis of p53-induced genes related to the onset of apoptosis ( 1 ). (ijbs.com)
  • 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)
  • A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
  • In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
  • In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. (icr.ac.uk)
  • Although intracellular signal transduction is often portrayed as a protein kinase 'domino effect', the counterbalancing function of phosphatases, and thus the control of phosphatase activity, is equally relevant to proper regulation of cellular function. (ac.be)
  • The cell cycle is a complex process with myriad genes involved and elaborate and complex signaling mechanisms to allow for this critical cellular process. (biomedcentral.com)
  • Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. (gsea-msigdb.org)
  • Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
  • In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)
  • Euchro matic, and thereby known, hyperacetylated controls were rep resented by the promoter and five coding areas of 27 cellular housekeeping genes. (sodiumchannel-signal.com)
  • 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)
  • Mammalian SNF5 is essential for normal cell viability, and loss or mutation of the human SNF gene is the molecular basis for familial malignant rhabdoid tumorigenesis. (umassmed.edu)
  • In this study, we have identified TIN2-R282H, the most common DC-causing mutation in shelterin subunit TIN2, as a separation-of-function mutant which impairs telomerase recruitment to telomeres, but not chromosome end protection. (prolekarniky.cz)
  • We screened for multicopy suppressors of a mutation in the nudF gene. (xenbase.org)
  • Our pipeline integrates three significant features, including mutation coverage in TCGA , driver mutation probability and the quantified cancer network information centrality, into a ranking model for SL gene pair identification, which is presented as the first learning-based method for SL identification. (oncotarget.com)
  • In particular, notable advances have been made in cancer therapy for example, with the discovery of Herceptin to treat breast cancer patients with HER2 amplification, and with Iressa for the treatment of non-small cell lung cancer patients with an EGFR mutation. (oncotarget.com)
  • Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. (bmbreports.org)
  • The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
  • DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
  • 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)
  • 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 direct link between DNA DSBs, genomic instability, and cancer is evidenced the fact that many cancer-predisposition syndromes in humans characterized by genomic instability are caused by mutations in DSB-responsive genes ( 16 , 17 ). (amegroups.org)
  • Cancer is fundamentally a genetic disease with numerous gene mutations involved. (oncotarget.com)
  • MCPH is inherited in an autosomal recessive pattern in which both copies of the gene in each cell have mutations. (biomedcentral.com)
  • However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
  • The risk is increased 1000-fold for squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and fibrosarcoma and is increased 10-fold to 20-fold for other tumors. (medscape.com)
  • Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD. (microbiologyresearch.org)
  • The phosphorylation of pRB, and relief of transcriptional repression by pRB induces genes involved in the induction of S-phase entry. (shu.edu)
  • Bovine leukemia virus (BLV) infects cattle, integrates into host DNA as a provirus, and induces malignant B-cell lymphoma. (biomedcentral.com)
  • Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
  • 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)
  • Turner Thomas and Caspari Thomas, 2014 , When heat casts a spell on the DNA damage checkpoints . (bangor.ac.uk)
  • 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)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. (biomedcentral.com)
  • Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated. (biomedcentral.com)
  • CDC2 gene plays an important role in the proliferation of human gliomas. (biomedcentral.com)
  • Downregulation of CDC2 could potentialy inhibit human gliomas cells growth ex vivo and in vivo. (biomedcentral.com)
  • From these results, it was suggested that CDC2 might be a potential target on gene therapy of human gliomas. (biomedcentral.com)
  • To reveal the roles of CDC2/Cyclin B1 in human malignant gliomas, CDC2 in glioma cell line, it was down-regulated by retrovirus vectors expressing short hairpin RNAs (shRNAs) ex vivo and in vivo. (biomedcentral.com)
  • Caspari T, Murray JM and Carr AM, 2002 , Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III. (bangor.ac.uk)
  • In the nucleus, R-SMAD-SMAD4 complexes cooperate with transcriptional coregulators that further define target gene recognition and transcriptional regulation. (shu.edu)
  • 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. (thno.org)
  • In some cell types, the photoreceptor protein cryptochrome (CRY) physically associates with TIM and helps regulate light-dependent degradation. (wikipedia.org)
  • First, given evidence that IGFs regulate the response to IR, we also found evidence that IGF-1R depletion induced endogenous DNA lesions marked by γH2AX foci in prostate cancer cells [ 10 ]. (nature.com)
  • Activated complexes accumulate in the nucleus where they cooperate with DNA-binding cofactors to regulate target gene transcription. (shu.edu)
  • One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. (gsea-msigdb.org)
  • To facilitate investigation of the mechanisms that control centrosome reproduction, a frog egg extract arrested in S phase of the cell cycle that supported repeated assembly of daughter centrosomes was developed. (umassmed.edu)
  • Multiple rounds of centrosome reproduction were blocked by selective inactivation of cyclin-dependent kinase 2-cyclin E (Cdk2-E) and were restored by addition of purified Cdk2-E. Confocal immunomicroscopy revealed that cyclin E was localized at the centrosome. (umassmed.edu)
  • These results demonstrate that Cdk2-E activity is required for centrosome duplication during S phase and suggest a mechanism that could coordinate centrosome reproduction with cycles of DNA synthesis and mitosis. (umassmed.edu)
  • We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays. (biomedcentral.com)
  • These pre-clinical models were used to observe cytotoxicity, cell cycle modulation and changes in gene expression to examine the mechanisms driving drug resistance. (biomedcentral.com)
  • In the mitosis, the chromosomes are aligned and the two sister chromatids are separated, each becoming the genetic material of the daughter cells. (androbose.in)
  • This gene encodes a protein phosphatase 1 binding protein. (nih.gov)
  • Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer. (nih.gov)
  • Biophysical Analysis of the N-Terminal Domain from the Human Protein Phosphatase 1 Nuclear Targeting Subunit PNUTS Suggests an Extended Transcription Factor TFIIS-Like Fold. (nih.gov)
  • The authors have previously reported that the Salmonella typhimurium SigD protein, a phosphatidylinositol phosphatase involved in invasion of the host cell, inhibits yeast growth, presumably by depleting an essential pool of phosphatidylinositol 4,5- bis phosphate, and also that a catalytically inactive version, SigD R468A , was able to arrest growth by a different mechanism that involved disruption of the actin cytoskeleton. (microbiologyresearch.org)
  • Timeless mRNA and protein oscillate rhythmically with time as part of a transcription-translation negative feedback loop involving the period (per) gene and its protein. (wikipedia.org)
  • This ends the PER/TIM repression of the CLK/CYC-mediated transcription of per and tim genes, allowing per and tim mRNA to be produced to restart the cycle. (wikipedia.org)
  • Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. (biomedcentral.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)
  • Transcription factors (TFs) drive gene expression programs that shape specific phenotypes [ 3 ], and are frequently dysregulated in cancer [ 4 ]. (aging-us.com)
  • Thus, MRs comprise typically a small number of TF-encoding genes (and their products) that control a disproportionate level of gene expression, giving rise to distinct molecular phenotypes associated with a particular disease. (aging-us.com)
  • Since the expression of genes defining discrete phenotypes is highly coordinated, application of reverse engineering algorithms to transcriptome datasets allows interpreting transcriptional networks by defining MRs and their associated regulons and gene circuits. (aging-us.com)
  • Our laboratory has a long-standing interest in immune signaling and cell metabolism underlying the differentiation and function of T cells, a central cell type in adaptive immunity and cancer immunotherapy. (stjude.org)
  • Lim SA, Su W, Chapman NM, Chi H . Lipid metabolism in T cell signaling and function. (stjude.org)
  • In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.com)
  • In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
  • Furthermore, HIF-1 actively limits the mitochondrial consumption of pyruvate at two levels: (i) through the enzyme PDK (PDH-kinase), which in turn inhibits PDH activity preventing the conversion of pyruvate into acetyl CoA, and thereby limiting mitochondrial metabolism of pyruvate [ 6 ] and (ii) through the direct activation of LDH [ 7 , 8 ]. (hindawi.com)
  • Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. (gsea-msigdb.org)
  • In eukaryotic cells the genetic material is surrounded by a membrane system called the nuclear envelope (NE). (brookes.ac.uk)
  • The Nuclear Envelope is a hallmark of eukaryotic cells. (brookes.ac.uk)
  • DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
  • Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. (biomedcentral.com)
  • PD-1 inhibition (Figure 1) has quickly become a front-line therapy for non-small cell lung cancer and melanoma . (shu.edu)
  • 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)
  • Second, growth inhibition by SigD R468A was mediated by a cell cycle arrest in G2 dependent on the Swe1 morphogenetic checkpoint, but SigD-induced growth inhibition was cell cycle independent. (microbiologyresearch.org)
  • Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1. (microbiologyresearch.org)
  • RUNX1‑RUNX1T1 suppression supported myeloid differentiation by the differential expression of CEBPA, CEBPE, ID2, JMJD6, IKZF1, CBFB, KIT and CDK6, while MAPK1 depletion inhibited the differentiation of t(8;21) cells by elevated expression of ADA and downregulation of JUN. (prinsesmaximacentrum.nl)
  • The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. (cancerindex.org)
  • 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)
  • Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. (nature.com)
  • 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)
  • We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell. (mdpi.com)
  • These studies unveiled a novel function of DNA-PKcs in safeguarding the genome integrity and cancer suppression as chromosomal instability (CIN) plays an important role in cancer development and is a hallmark of cancer cells ( 14 ). (amegroups.org)
  • Carcinogenesis is a multi-step process wherein abrogation of multiple cancer susceptibility genes leads to cancer development. (amegroups.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)
  • Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. (gsea-msigdb.org)
  • Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. (gsea-msigdb.org)
  • 13 Genome Plasticity and B Cell, University of Paris-Sud, Centre National de la Recherche Scientifique, Cancer Institute Gustave Roussy, Villejuif, France. (jci.org)
  • DNA repair targeted therapy, which kills cancer cells preventing DNA repair [1-3]. (termedia.pl)
  • These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
  • CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)
  • 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)
  • Most cancer cells have PD-L1 on their surface and escape being killed by turning off the T cell in this way. (shu.edu)
  • PD-1 expression by cancer cells blocks the proliferation of T-cells. (shu.edu)
  • Here, we evaluated the efficacy of ST on three different human cancer cell lines including skin epidermoid carcinoma A431 cells, lung epithelial carcinoma A549 cells and breast adenocarcinoma MDA-MB-231. (biomedcentral.com)
  • Cell growth assay, cell cycle analysis, FACS, JC-1 staining, annexin V staining and immunoblotting were used to study the efficacy of ST on cancer cells. (biomedcentral.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)
  • This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. (biomedcentral.com)
  • Human ovarian cancer cell lines TOV21G (representing clear cell ovarian carcinoma) and TOV112D (representing endometrioid adenocarcinoma) were purchased from American Type Culture Collection (Manassas, VA). The human ovarian epithelial-serous cell line COV504 was purchased from Sigma Aldrich (St. Louis, MO). (biomedcentral.com)
  • In this study, we propose an efficient and comprehensive in-silico pipeline to rank novel SL gene pairs by mining vast amounts of accumulated tumor high-throughput sequencing data in The Cancer Genome Atlas (TCGA), coupled with other protein interaction networks and cell line information. (oncotarget.com)
  • In addition, 4 SL pairs, mTOR-TP53, VEGFR2-TP53, EGFR-TP53, ATM-PRKCA, were validated using drug sensitivity information in the cancer cell line databases CCLE or NCI60 . (oncotarget.com)
  • Interestingly, significant differences in the cell growth of mTOR siRNA or EGFR siRNA knock-down were detected between cancer cells with wild type TP53 and mutant TP53. (oncotarget.com)
  • Our study indicates that the pre-screening of potential SL gene pairs based on the large genomics data repertoire of tumor tissues and cancer cell lines could substantially expedite the identification of synthetic lethal gene pairs for cancer therapy. (oncotarget.com)
  • Caspari Thomas, 2015 , How cancer abducts your immune cells - and what we can do about it. (bangor.ac.uk)
  • Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. (bmbreports.org)
  • This is why only isolated DNA repair signaling is inactivated in cancer cells. (bmbreports.org)
  • Metabolic adaptations of cancer cells. (hindawi.com)
  • Glucose and glutamine are the 2 major substrates used by cancer cells. (hindawi.com)
  • Table 1 provides a summary outline of the gene symbols, chromosomal locations, radiation sensitivity characteristics, immunodeficiencies, chromosome breakage characteristics, and major cancer risk for each of these disorders. (medscape.com)
  • The top 14 hub genes were subsequently confirmed by reverse transcription‑quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. (cancerindex.org)
  • The multi-subunit shelterin complexes bind along mammalian telomeres, shielding the natural chromosome ends from engaging the DNA damage signaling and repair machinery [ 1 ]. (prolekarniky.cz)
  • 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)
  • T cell receptor beta co. (gsea-msigdb.org)
  • 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)
  • If you are a Human Resources kinase, this response ought to be on a complex in your receptor. (familie-vos.de)
  • The timeless gene is an essential component of the molecular circadian clock in Drosophila. (wikipedia.org)
  • Reuben J. Shaw, Howard Hughes Medical Institute, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037. (aacrjournals.org)
  • In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.com)
  • Nat Cell Biol 24(7):1154-1164, 2022. (mdanderson.org)
  • Nat Cell Biol, 2017 Sep. (nih.gov)
  • Mol Cell Biol. (bangor.ac.uk)
  • Nat Cell Biol 24:1642-1654, 2022 (highlighted by News and Views "PTEN checkMAITs type-17 innate-like T cells" in the same issue). (stjude.org)
  • Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. (nature.com)
  • RUNX1‑RUNX1T1 and MAPK1 depletion induced cell cycle arrest at the G0/G1 phase. (prinsesmaximacentrum.nl)
  • Accumulation of cells in the G1 phase was largely the result of downregulated expression of TBRG4, CCNE2, FOXO4, CDK6, ING4, IL8, MAD2L1 and CCNG2 in the case of RUNX1‑RUNX1T1 depletion and increased expression of RASSF1, FBXO6, DADD45A and P53 in the case of MAPK1 depletion. (prinsesmaximacentrum.nl)
  • Our results are the first to demonstrate clonal expansion after the massive depletion of cells carrying BLV integration sites in a naturally infected cow. (biomedcentral.com)
  • In normal cells, the fate of pyruvate depends on many factors, one of which is oxygen availability. (hindawi.com)
  • Inside the mitochondria, pyruvate is completely oxidized through the TCA cycle, feeding reductive equivalents to the electron transport chain. (hindawi.com)
  • When oxygen is limited, as in muscles that have undergone prolonged exercise, pyruvate is not consumed in the TCA cycle but is rather converted into lactic acid by lactate dehydrogenase (LDH) in a process termed anaerobic glycolysis. (hindawi.com)
  • Furthermore, these three genes predicted overall survival and recurrence‑free survival in patients with ACC from the TCGA cohort. (cancerindex.org)
  • Several cell cycle events require specific forms of the cyclin-CDK complexes. (umassmed.edu)
  • If you go in page, at the platelets of the checkpoint or cytosol, this maturation will Learn a negative energy to be yourself with the available synthesis of complexes that you will be every factor. (familie-vos.de)
  • Although immune checkpoint inhibitors (ICIs), in particular blockade of PD-1/PD-L1, show promising therapy response in some cancers, they are less effective in PCa which may be poor infiltration of cytotoxic T-cells [ 7 - 9 ]. (thno.org)
  • Between clonal expansion and cell proliferation, the survival of infected cells requires the silencing of viral expression before the immune response. (biomedcentral.com)
  • Our laboratory has made important discoveries in understanding the principle of metabolic reprogramming for immune cell fate, state and tolerance. (stjude.org)
  • Typically, rapidly proliferating tumor cells have glycolytic rates up to 200 times higher than those of their normal tissue of origin, even in the presence of oxygen [ 3 ]. (hindawi.com)
  • Cells in the G0 phase are ones that have entered a non-dividing state either reversibly or irreversibly . (androbose.in)
  • The irreversibly non-dividing cells either become senescent or differentiated. (androbose.in)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • Interphase is the phase in which the cell grows till it can divide it's genetic material and the cytoplasm into two halves i.e. capable of producing two daughter cells. (androbose.in)
  • Xu et al, Genes Dev 31, 1469-1482, 2017 ) Visit Dr. Wang's lab website . (mdanderson.org)
  • Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
  • Since strong consensus regarding commonly altered MRs in hepatocellular carcinoma (HCC) is lacking, we generated a compendium of HCC datasets from 21 studies and identified a comprehensive signature consisting of 483 genes commonly deregulated in HCC. (aging-us.com)
  • Finally, we showed that ssDNA lesions are converted to toxic DSBs in cells lacking functional ataxia telangiectasia mutated (ATM), likely due to failure to form 53BP1 bodies and/or a role for ATM in SSB repair or fork protection [ 14 ]. (nature.com)
  • The PER/TIM heterodimer negatively regulates transcription of period (per) and timeless (tim) genes. (wikipedia.org)
  • The complex then blocks the positive transcription factors clock (CLK) and cycle (CYC), thereby repressing the transcription of per. (wikipedia.org)
  • This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. (cancerindex.org)
  • 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)
  • This spot also contains a gene with powerful homology for the family of dihydrofolate re ductases, even so, its transcription seems unaffected by histone acetylation, considering that expression of this gene can't be detected. (sodiumchannel-signal.com)
  • As a result, 107 potential SL gene pairs were obtained from the top 10 results covering 11 cancers. (oncotarget.com)