• DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7. (wikipedia.org)
  • DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase called DNA-PK. (wikipedia.org)
  • The core NHEJ machinery includes XRCC4, DNA ligase IV and the DNA-dependent protein kinase complex, which consists of the DNA end-binding XRCC5/XRCC6 heterodimer and the catalytic subunit PRKDC. (ptglab.com)
  • This rigorous examination revealed seven overlapping proteins (Fig.?1e): DDX21, Ku80, SUPT16H, proteins kinase DNA-activated catalytic subunit (PRKDC), histones H4 and H2B, and chromatin SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5). (cell-signaling-pathways.com)
  • we confirmed that the expression of several key proteins among the 296 proteins, including UHRF1, DExD-Box Helicase 21 (DDX21), and SPT16 21-Hydroxypregnenolone homolog facilitates chromatin remodeling subunit (SUPT16H), was almost the same in the input of WT and KO cells, which excludes the possibility that these proteins were only decreased in the KO cells (Supplementary Fig. S1). (cell-signaling-pathways.com)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase related kinase family is a well-known player in repairing DNA double strand break through non-homologous end joining pathway. (molcells.org)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), encoded by PRKDC gene, is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, which also includes the two DNA damage repair proteins, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein (ATR). (molcells.org)
  • 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)
  • On germline analysis, they identified a rare variant affecting PRKDC , protein kinase DNA-activated catalytic polypeptide (DNA-PKcs). (medscape.com)
  • The DNA-Pkcs protein is a serine/threonine protein kinase consisting of a single polypeptide chain of 4,128 amino acids. (wikipedia.org)
  • DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect. (wikipedia.org)
  • Thus, deficiency in DNA-PKcs activity results in a severe combined immunodeficiency (SCID) phenotype in mammals ( 3 - 5 ). (amegroups.org)
  • DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. (wikipedia.org)
  • This phosphorylation is regulated by the ataxia telangiectasia mutated (ATM) and the Rad3-related (ATR) kinases in response to various genotoxic stresses, making it a critical regulatory element of DNA-PKcs ( 6 , 10 ). (amegroups.org)
  • Description: A sandwich ELISA kit for detection of Protein Tyrosine Phosphatase, Non Receptor Type 11 from Rat in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (worldcarecouncil.org)
  • Description: A sandwich ELISA kit for detection of Cold Shock Domain Containing Protein E1, RNA Binding from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (worldcarecouncil.org)
  • Description: A sandwich ELISA kit for detection of Dynein Heavy Chain Domain Containing Protein 1 from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (youngresearch.eu)
  • RFA2 is absolutely required for simian virus 40 DNA replication in vitro. (affbiotech.com)
  • Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. (biomedcentral.com)
  • Nck-associated protein 1 (NAP1/NCKAP1), a protein that associates with the Src homology 3 (SH3) domain of NCK protein both in vitro and in intact cells, was found to localize along the lamellipodia and to mediate contact-dependent cell migration [ 4 ]. (biomedcentral.com)
  • Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. (sagepub.com)
  • Additionally, a protein-protein interaction (PPI) network was constructed to identify key genes involved in enhanced X-ray susceptibility of FaDu cells treated with RITA. (sagepub.com)
  • Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis. (biomedcentral.com)
  • Mitochondrial transplantation also consistently decreased Drp-1, which resulted in an enhancement of the tubular mitochondrial network, but a distinct machinery through the increase of parkin and mitochondrial fusion proteins was observed in the Mito and P-Mito groups, respectively. (biomedcentral.com)
  • Our findings suggest that the CDCA7/HELLS complex mediates a multi-layered protection mechanism by regulating maintenance DNA methylation, the resolution or prevention of DNA:RNA hybrids (R-loops), and DNA repair at pericentromeric satellite repeats. (cell-signaling-pathways.com)
  • Results Proteins involved in maintenance DNA methylation and R-loop resolution/prevention are decreased on nascent DNA in the absence of CDCA7 We hypothesized that the CDCA7/HELLS complex could 21-Hydroxypregnenolone play a role in facilitating maintenance DNA methylation at pericentromeric repeats by recruiting DNA methylation maintenance factors. (cell-signaling-pathways.com)
  • This result is consistent with our hypothesis that CDCA7 could be involved in maintenance DNA methylation in specific genomic regions, possibly heterochromatic and late replicating regions15,16. (cell-signaling-pathways.com)
  • Open in a separate window Figure 1 Proteins involved in maintenance DNA methylation and R-loop resolution/prevention are decreased on nascent DNA in the absence of CDCA7. (cell-signaling-pathways.com)
  • That is, in ATM-mutant cells, an inhibitor of DNA-PKcs causes high levels of apoptotic cell death. (wikipedia.org)
  • Mechanistically, we identified the Inhibitor of DNA binding 1 and 3 ( ID1, ID3 ), drivers of cancer stemness and plasticity, as previously uncharacterized targets of transcriptional repression by ZNF148. (nature.com)
  • The Inhibitor of DNA binding 3 ( ID3 ) is a member of the ID protein family, consisting of four members ( ID1 to ID4 ). (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)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Protein Tyrosine Phosphatase, Non Receptor Type 11 (PTPN11) in samples from tissue homogenates or other biological fluids. (worldcarecouncil.org)
  • The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). (aopwiki.org)
  • Epigenetic reduction or absence of let-7a microRNA allows high expression of the HMGA2 protein and this would lead to defective expression of DNA-PKcs. (wikipedia.org)
  • While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. (molcells.org)
  • syndromes', each of which results from a defective response to a specific DNA lesion. (diff.org)
  • In response to DSB formation, DNA-PKcs is recruited to DSBs by the DNA end-binding Ku70/80 heterodimer and is rapidly phosphorylated at multiple serine and threonine residues ( 1 , 2 ). (amegroups.org)
  • Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break. (wikipedia.org)
  • coordinates DNA repair by activating enzymes that fix the broken strands. (diff.org)
  • Prenatal diagnosis involves testing the DNA of fetal or placental cells, obtained through chorionic villous sampling (CVS), amniocentesis, or non-invasive means, to see if the SCID-causing genetic variant is present. (primaryimmune.org)
  • Twenty-four non-ovariectomized female SCID mice (BALB/cJHan®Hsd- Prkdc scid , Harlan Laboratories Models, S. L.), 6-8 weeks of age and weighing between 20 and 22 g were used. (biomedcentral.com)
  • Antibodies bound to the blocking peptide no longer bind to the epitope on the target protein. (affbiotech.com)
  • DNA-PKcs is required for the non-homologous end joining (NHEJ) pathway of DNA repair, which rejoins double-strand breaks. (wikipedia.org)
  • When cancer cells are deficient in ATM the cells are "addicted" to DNA-PKcs, important in the alternative DNA repair pathway for double-strand breaks, non-homologous end joining (NHEJ). (wikipedia.org)
  • In ATM mutant cells, additional loss of DNA-PKcs leaves the cells without either major pathway (HRR and NHEJ) for repair of DNA double-strand breaks. (wikipedia.org)
  • There are at least two pathways for eukaryotes to repair DNA double-strand breaks: homologous recombination and nonhomologous end joining(NHEJ). (ptglab.com)
  • DNA-PKcs and the NHEJ pathway are also essential for V(D)J recombination during T and B cell lymphocyte development. (amegroups.org)
  • Activating transcription factor 4 (ATF4) plays an important role in regulating glucose and lipid metabolic homeostasis in hepatocytes and adipocytes. (bvsalud.org)
  • We demonstrated that abnormal transcription from hypomethylated pericentromeric satellite repeats and the formation of aberrant DNA:RNA hybrids occur in ICF mutant cells and presumably trigger DNA damage. (cell-signaling-pathways.com)
  • Below is a small sample of the many proteins, growth factors, transcription factors it contains. (plurisomes.com)
  • p53 is a DNA-binding protein containing DNA-binding, oligomerization and transcription activation domains. (affbiotech.cn)
  • Such excess DNA damage may increase mutations due to error-prone translesion synthesis. (wikipedia.org)
  • PRKDC (DNA-PKcs) mutations were found in 3 out of 10 of endometriosis-associated ovarian cancers, as well as in the field defects from which they arose. (wikipedia.org)
  • protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (diff.org)
  • this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
  • 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)
  • encodes a protein that transcriptionally activates (also known as (also known as KO cells. (cell-signaling-pathways.com)
  • The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. (affbiotech.cn)
  • DNA-PKcs phosphorylation at Ser2056, on the other hand, is primarily mediated by autophosphorylation, making it an excellent marker to monitor DNA-PKcs activation in vivo ( 11 ). (amegroups.org)
  • Fresh mitochondria isolated from homeoplasmic 143B osteosarcoma cybrids containing mitochondrial DNA (mtDNA) derived from health individuals (Mito) or mtDNA with the A8344G mutation (Mito 8344 ) were conjugated with cell-penetrating peptide Pep-1 (P-Mito) or not conjugated prior to cell co-culture. (biomedcentral.com)
  • Involved in replication and repair of r DNA and in repairing mitochondrial DNA . (plurisomes.com)
  • 198) on nascent DNA in knockout (KO) HEK293 cells compared with wild-type (WT) HEK293 cells, as determined by the isolation of proteins on nascent DNA (iPOND)Ctandem mass spectrometry (MS/MS) analysis. (cell-signaling-pathways.com)
  • Tumor protein p53, a nuclear protein, plays an essential role in the regulation of cell cycle, specifically in the transition from G0 to G1. (affbiotech.cn)
  • HMGA2 delays the release of DNA-PKcs from sites of double-strand breaks, interfering with DNA repair by non-homologous end joining and causing chromosomal aberrations. (wikipedia.org)
  • This lymphoma is caused by chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK). (biomedcentral.com)
  • We performed CRISPR/Cas9-mediated genome editing of the NPM-ALK chromosomal translocation in primary human activated T lymphocytes. (biomedcentral.com)
  • Between 60 and 80% of ALK+ ALCL cases harbor the NPM-ALK chromosomal translocation, which leads to constitutive activation of the ALK protein. (biomedcentral.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)
  • After ionizing radiation DNA-PKcs was increased in the surviving cells of oral squamous cell carcinoma tissues. (wikipedia.org)
  • Elevated DNA-PKcs is thought to be "beneficial to the tumor cells", though it would be at the expense of the patient. (wikipedia.org)
  • expression of RNASEH1 reduced the accumulation of DNA damage at a broad range of genomic regions including pericentromeric repeats in these cells. (cell-signaling-pathways.com)
  • A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the accumulation of proteins involved in the spliceosome (KO cells (Fig.?1c and Supplementary Table S3). (cell-signaling-pathways.com)
  • Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level. (molcells.org)
  • have reported that increased DNA-PKcs activity can suppress HR repair in G1 phase of cells through increasing RBX1 protein expression, which prompts the neddylation and activity of cullin 1, a key component of the Skp1-Cullin1-F-box ubiquitin 3 ligase, consequently mediating ubiquitination and degradation of EXO1. (molcells.org)
  • cells in recognizing damaged or broken DNA strands. (diff.org)
  • many of the body's cells from correctly repairing damaged DNA. (diff.org)
  • Cells that are missing one copy of the ATM gene produce half the normal amount of ATM protein. (diff.org)
  • In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. (oncotarget.com)
  • Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells. (biomedcentral.com)
  • Our previous studies further demonstrated that NAP1 is required for the protein stability of WASF3 in breast cancer cells, implicating that NAP1 is a critical regulator in favor of breast cancer metastasis [ 5 ]. (biomedcentral.com)
  • Several forms of cell death include apoptosis, necrosis, and autophagy, which differ mainly in the cells morphological changes that accompany them, as well as the proteins involved in their activation and execution. (epigentek.com)
  • The serine-threonine kinase 1 (AKT1)/mammalian target of rapamycin (mTOR) axis is involved in melanoma progression. (bvsalud.org)
  • Intermittent administration of vemurafenib and cobimetinib has durably maintained a near-complete melanoma response and has prevented CMML progression in association with decreased levels of CMML-derived circulating tumor DNA and reduced ERK activation in monocytes. (aacrjournals.org)
  • One such discovery, which has probably been pivotal in many of our research, is the discovery of the green fluorescent protein (GFP) , commonly used as an invaluable tool to monitor protein for cellular expression and localization studies. (pharmaceuticalintelligence.com)
  • Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. (molcells.org)
  • and cellular phenotype that is caused by ATM loss clearly places this protein at a top position in the DSB -response cascade. (diff.org)
  • Plays a central role in DNA repair by facilitating cellular responses to DNA damage. (plurisomes.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)
  • It usually involves activation of caspases, and is commonly divided into intrinsic or extrinsic pathways, depending on whether it is activated by the mitochondria with subsequent release of cytochrome C (intrinsic apoptotic pathway) or whether it is activated by death receptors (extrinsic apoptotic pathway). (epigentek.com)
  • MicroRNA-101 targets DNA-PKcs via binding to the 3'- UTR of DNA-PKcs mRNA and efficiently reduces protein levels of DNA-PKcs. (wikipedia.org)
  • The mRNA and protein levels were measured via qRT-PCR and Western blotting. (bvsalud.org)
  • Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. (biomedcentral.com)
  • In normal adult tissues, almost no HMGA2 protein is present. (wikipedia.org)
  • Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. (biomedcentral.com)
  • On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity. (wikipedia.org)
  • DNA damage appears to be the primary underlying cause of cancer, and deficiencies in DNA repair genes likely underlie many forms of cancer. (wikipedia.org)
  • Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. (wikipedia.org)
  • Reductions in expression of DNA repair genes (usually caused by epigenetic alterations) are very common in cancers, and are ordinarily even more frequent than mutational defects in DNA repair genes in cancers. (wikipedia.org)
  • The ATM protein is important in homologous recombinational repair (HRR) of DNA double strand breaks. (wikipedia.org)
  • The elevation of DNA-PKcs is thought to reflect the induction of a compensatory DNA repair capability, due to the genome instability in these cancers. (wikipedia.org)
  • As indicated in the article Genome instability, such genome instability may be due to deficiencies in other DNA repair genes present in the cancers. (wikipedia.org)
  • Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (diff.org)
  • Involved in the repair of damaged DNA . (plurisomes.com)
  • Protein, which is both involved in DNA repair and protein ubiquitination. (plurisomes.com)
  • DNA-PKcs phosphorylation at the Thr2609 cluster region is particularly significant since it is critical for DSB repair and radioresistance ( 6 - 9 ). (amegroups.org)
  • The following is a heartwarming story by Discover Magazine's Yudhijit Bhattacharjee behind Dr. Douglas Prasher's discovery of the green fluorescent protein, his successful efforts to sequence the gene and subsequent struggles in science and finally scientific recognition for his work. (pharmaceuticalintelligence.com)
  • Briefly, 5-ethynyl-2-deoxyuridine (EdU), which contains an alkyne, was incorporated into newly synthesized nascent DNA in place of thymidine, proteins and DNA were cross-linked using formaldehyde, and biotin was conjugated to the incorporated EdU via the azide-alkyne cycloaddition. (cell-signaling-pathways.com)
  • As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. (affbiotech.com)
  • citation needed] DNA-PKcs expression was reduced by 23% to 57% in six cancers as indicated in the table. (wikipedia.org)
  • It is not clear what causes reduced expression of DNA-PKcs in cancers. (wikipedia.org)
  • Elevated DNA-PKcs expression is found in a large fraction (40% to 90%) of some cancers (the remaining fraction of cancers often has reduced or absent expression of DNA-PKcs). (wikipedia.org)
  • As indicated in a table listing 12 types of cancer reported in 20 publications, the fraction of cancers with over-expression of DNA-PKcs is often associated with an advanced stage of the cancer and shorter survival time for the patient. (wikipedia.org)
  • Before leaving Wood's Hole he gave the gene to Dr. Roger Tsien, who with Dr. Martin Chalfie and Osamu Shimomura showed the utility of GFP as an intracellular tracer to visualize, in real time, the expression and localization of GFP-tagged proteins (all three shared the 2008 Nobel Prize for this work). (pharmaceuticalintelligence.com)
  • Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. (oncotarget.com)
  • Clinical studies indicate that expression and activity of DNA-PKcs is correlated with cancer progression and response to treatment. (amegroups.org)
  • It is postulated to bind as a tetramer to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. (affbiotech.cn)
  • Anaplastic large cell lymphoma with anaplastic lymphoma kinase gene translocations (ALK+ ALCL) is a mature T-cell lymphoma that primarily affects lymph nodes, but also gives rise to tumors in extranodal organs and occasional characteristic skin lesions. (biomedcentral.com)