Ku70 S155D was found to interact with Aurora B and to have an inhibitory effect on Aurora B kinase activity. Lastly, we demonstrate that Ku and Aurora B interact following ionizing radiation treatment and that Aurora B inhibition in response to DNA damage is dependent upon Ku70 S155 phosphorylation.

The DNA-PK inhibitor, NU7441, could significantly inhibit DNA-PK and Ku70 expression, simultaneously further aggravating BP-induced apoptosis and DNA damage under high-glucose conditions. CONCLUSION: These data indicate that hyperglycaemia may enhance BP-induced neurotoxicity and DNA damage by inhibiting the DNA repair protein Ku70.

We here describe an in silico, pocket-based drug discovery methodology utilizing the crystal structure of the Ku70/80 heterodimer. Upon HDACI treatment, acetylated Ku70 releases Bax, allowing it to translocate to mitochondria and trigger cytochrome c release, leading to caspase-dependent death. This study shows that Ku70 is an important Bax-binding protein, and that this interaction can be therapeutically regulated in NB cells. Ku70 is a protein that repairs DNA breaks and stabilizes anti-apoptotic protein c-FLIP and proapoptotic protein Bax, which is regulated by acetylation. HDAC inhibitors induce Ku70 acetylation with repressed c-FLIP and activated Bax in cancer cells.

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The INHAT (inhibitor of histone  22 Jun 2010 Immunoblotting, luciferase reporter assays, and flow cytometry showed that Ku70 inhibited FOXO4‐mediated p27kip1 transcription and cell  Ku70 is a protein that, in humans, is encoded by the XRCC6 gene. Contents. 1 Function; 2 Aging; 3 Clinical; 4 Nomenclature; 5 Interactions; 6 References  sequence of Bax-binding domain of human Ku70, and showed that these peptides bind Bax and inhibit cell death in human cell lines. In the present report, we  Consequently, inhibition of the NHEJ pathway can modulate a radiation- or chemo-refractory disease presentation. The Ku70/80 heterodimer protein plays a   Additionally, we demonstrate that the Ku70 S155D vWA domain is sufficient to inhibit Aurora B in an in vitro kinase assay. Finally, Aurora B inhibitor treatment of   29 Oct 2018 In addition, silencing Ku70 inhibited the pro-proliferative effect by Sirt3.

2014-04-11 · This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings 2017-11-24 · Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition.

5 Följaktligen RNA-transkription inhibition är ett bra sätt att identifiera foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II.

Furthermore, acetyl-Ku70 promoted the dissociation of Ku-70 from BAX, thus promoting BAX-dependent cell apoptosis (Fig. 3e, f).

2020-12-01

In our study, MPT0G211 induced Ku70 acetylation. This led to the sequestration of Ku70 in the cytosol, which blocked its binding to double-strand breaks (Fig. 3c, d Ku70 significantly inhibited FOXO4‐mediated cell cycle arrest, in agreement with the luciferase reporter assay and the inhibition of p27 kip1 transcriptional activity. Finally, we tested the endogenous role of Ku70 on FOXO4 transcriptional targets by employing RNA interference.

av K Söderlund Leifler · 2009 — some of these pro- teins with inhibitory drugs to sensitise tumours to radiotherapy. binding to Ku70/80, DNA-PKcs is activated by autophosphorylation and. the heterodimeric Ku70/86, and a catalytic subunit known as DNA-dependent function of DNA-PK, causing a dominant-negative inhibition of DNA repair. Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer2010Ingår i: INTERNATIONAL  Rapid recruitment of PR-Set7 to DSBs was dependent on the NHEJ Ku70 Their findings suggest that inhibition of H4K20me may be useful in epigenetic  aktivera Bax, genom att klyva och inaktivera inhibitorer av Bax (14-3-3θ och Ku70).
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111In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer. 9 sep. 2019 — föreslagna möjligheten till anstånd skulle den enskilde behöva ansöka om inhibition av beslutet med förvaltningsrätten som första instans. Rättsprövningslagens bestämmelse om inhibition har i huvudsak samma Ku. 70.

STL127705 also inhibits Ku-dependent activation of DNA-PKCS kinase (IC50, 2.5 μM).
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decreased p65 inhibition, along with increased phosphorylation and nuclear PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four 

An increase in ubiquitinated Ku70 protein was observed in apoptotic cells, and proteasome inhibitors attenuated the decrease in Ku70 levels in apoptotic cells. These results suggest that the ubiquitin–proteasome proteolytic pathway plays a role in decreasing Ku70 levels in apoptotic cells. Ku70 is known to be a repair protein as well as an inhibitor of apoptosis through its association with Bax . The results of the present study have also demonstrated that TSA induced cell death in CRC cells through increasing the acetylation of Ku70, a Bax-binding protein, which therefore promoted Bax release and translocation from the cytoplasm into mitochondria in order to stimulate apoptosis.