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貨期:
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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ. Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
基因功能參考文獻:
Small cell lung cancer (SCLC) subtype had amplified risk with XRCC7 6721G>T. Gene-environment interaction analysis revealed that XRCC6 61C>G showed a strong protective effect towards lung cancer. Survival analysis revealed poor prognosis in case of XRCC6 61C>G SCLC subtype. XRCC7 6721G>T subjects with SCLC subtype showed an increased susceptibility while poor prognosis in case of XRCC6 61C>G. PMID: 29397516
Loss of DNA-PKc expression is associated with impairment of non-homologous end-joining of radiation-induced double strand break repair in nasopharyngeal carcinoma. PMID: 29344644
DNA-dependent protein kinase plays a central role in transformation of breast epithelial cells following alkylation damage. PMID: 28923836
miRNA-101 level is decreased in RCC tissues/cells, which could be responsible for DNA-PKcs overexpression and DNA-PKcs mediated oncogenic actions; DNA-PKcs over-expression regulates mTORC2-AKT activation, HIF-2alpha expression and RCC cell proliferation PMID: 27412013
The study reveals a structural basis for the complex assembly of DNA-PK and an allosteric mechanism for the activation of DNA-PKcs. PMID: 28840859
DNA-PK holoenzyme cryo-EM map reveals density for the C-terminal globular domain of Ku80 that interacts with the arm of DNA-PKcs PMID: 28652322
Data indicate that abnormal ERGIC1 and DNA-PKcs expression may play an important role in gastric cancer initiation. PMID: 28970727
The crystal structure defines a stage on which many of the components assemble and regulate the kinase activity through modulating the conformation and allosteric regulation of kinase activity. PMID: 28668119
downregulation of PRKDC sensitized MCF-7 cells to chemo-drugs both in vitro and in a xenografted mouse model. Collectively, our study demonstrated that PRKDC is a prognostic biomarker for chemoresistance in breast cancer patients. PMID: 28498431
Down-regulation of PRKDC attenuates tumor progression in prostate cancer (PCa). PRKDC may potentially be a prognostic biomarker in PCa. PMID: 27856181
Suggest that IL-10 rs1800871 and PRKDC rs7003908 may be useful biomarkers for predicting glioma patient survival. PMID: 27811370
Results provide evidence that DNA-PKcs is a primary resistance factor of salinomycin in osteosarcoma cells. PMID: 27765904
This study showed that the levels of CD44 and DNA-PK are associated with a better survival and better response to radiotherapy and temozolomide. PMID: 28070830
this study suggests that improved anti-proliferative and cytotoxic effects of Ag-np treatment in cancer cells can be achieved by the inhibition of DNA-PKcs. PMID: 29150048
this study has solved the PRKDC structure in complex with the C-terminal peptide of Ku80 at 4.3 angstrom resolution using x-ray crystallography. PMID: 28154079
DNA-PKcs, which is integral to the non-homologous end joining pathway, negatively regulates ATM activity through phosphorylation of ATM. PMID: 27939942
that EZH2 is phosphorylated by the DNA damage responsive complex DNA-PK and regulates DNA damage-mediated T-cell apoptosis. PMID: 27468692
DNA-PKcs is a potent regulator of IL-2 production in T lymphocytes. PMID: 28750002
TMU-35435 enhances etoposide cytotoxicity by regulating ubiquitin-proteasomal degradation of DNA-PKcs and inhibiting the DNA repair pathway in triple negative breast cancer cells. PMID: 28450160
DNA-PK directly phosphorylates hSSB1 at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. PMID: 28448822
DNA-PK activity in peripheral blood lymphocytes might be a useful marker for predicting prostate-specific antigen relapse and urinary toxicity, possibly contributing to personalized treatment of prostate cancer. PMID: 28399576
Data suggest that the model can replicate amplified p53 responses under DNA-PK inhibition and provide insights into cell fate decision by manipulating p53 dynamics. PMID: 28177883
These studies clarify the role of PKCdelta in endothelial cell cytoskeleton regulation. PMID: 27442243
T204 was identified as a main target for ATM/DNA-PKcs phosphorylation on human POLL, and this phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient POLL-mediated gap-filling during NHEJ. POLL phosphorylation might favor POLL interaction with the DNA-PK complex at DSBs. PMID: 28109743
DNA-PKcs inhibitor acriflavine exerts a p53-dependent synergistic efficacy with melphalan against human cancer cells both in vitro and in vivo. PMID: 27693638
EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma. PMID: 27255972
Together, our results provide evidence that acetylation potentially regulates DNA-PKcs. PMID: 27297111
Inhibiting PRKDC radiosensitizes human osteosarcoma cells. PMID: 28300555
these results suggest that miR-101 sensitizes pancreatic cancer cells to gemcitabine possibly via downregulating DNA-PKcs. PMID: 27988337
The bocavirus large viral nonstructural protein NS1 is sufficient to induce the DNA damage response and the activation of the host ATM, ATR, and DNAPK. PMID: 27733644
inhibition of DNAPKcs decreases Pgp expression and sensitizes osteosarcoma cancer stem cells to chemotherapeutic agents in vitro PMID: 27499034
These results suggested potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells. PMID: 26666690
Data show that elevated expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Akt3 protein, and tumor suppressor protein p53 (p53) in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis. PMID: 27629740
CDK2 and DNA-PK regulate PR transcriptional activity by distinct mechanisms. PMID: 26652902
Results show that under hypoxia, Ku70 and DNA-PKcs interact with nuclear RON which activates non-homologous end joining DNA repair conferring chemoresistance. PMID: 26772202
A significantly different distribution was found in the frequency of PRKDC (rs7003908) genotype between the ESCC group and controls. Individuals homozygous for the C allele had a significant (3.185-fold) increased risk of ESCC. PMID: 26166223
Transient knockdown of PRKDC reduced cell proliferation/survival in HCT116 and DLD1, but not FHC cells. PRKDC down-regulation induced apoptosis partially through inhibiting AKT activation, and sensitized HCT116 cells to chemotherapeutic agents PMID: 26992638
DNA methylation modification plays an important role to regulate the gene expression of XRCC5 and XRCC7, from the results that the gene methylation level of the glioma group is higher than that of the normal group PMID: 26464705
The ends are then closely aligned, which requires XLF, a non-catalytic function of XRCC4-LIG4, and DNA-PK activity PMID: 26990988
suggested that DNA-PK and PARP-dependent recruitment of XRCC1 is necessary to effectively protect, repair, and restart stalled replication forks, providing new insight into how genomic stability is preserved PMID: 26603896
Data show that inhibition of DNA-dependent protein kinase catalytic subunit (DNA-PK) prevents type I DNA topoisomerase (Top1) degradation and proteasome activity in camptothecin (CPT)-treated quiescent WI38 cells. PMID: 26578593
protein deficiency impairs Ig class switch recombination PMID: 26546606
These results provide new evidence linking cell cycle to bystander responses and demonstrate that DNA-PKcs and ATM are two associated factors in co-regulating G2-M phase-related bystander effects. PMID: 26774662
c-Myc protein functions in the process of DNA double-strand break repair, at least partially, through affecting the ATM phosphorylation and DNA-PKcs kinase activity. PMID: 26049366
DNA-PKcs has a role in cancer metastasis through regulation of secreted proteins involved in migration and invasion PMID: 26017556
Results show that activated DNA-PKcs is elevated in medullary thyroid tumor samples and its expression correlates with expression of RET in thyroid tumors. PMID: 26065416
Our study supported that DNA-PKcs was involved in drug-induced DNA damage repair and related to chemosensitivity of osteosarcoma MG63 cells PMID: 26108997
Kaposi's sarcoma-associated herpesvirus appears then to selectively activate DNA damage response pathways via the ATM and DNA-PK DNA damage response kinases. PMID: 26057167
BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy. PMID: 25205036
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相關疾病:
Immunodeficiency 26 with or without neurologic abnormalities (IMD26)