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

av K Söderlund Leifler · 2009 · 1 MB — some of these pro- teins with inhibitory drugs to sensitise tumours to radiotherapy. binding to Ku70/80, DNA-PKcs is activated by autophosphorylation and.

As a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, DNA-PK is best known as a mediator of the cellular response to DNA damage. In this context, DNA-PK has emerged as an intriguing therapeutic target in the treatment of a variety of cancers Ku70 acetylation results in the dissociation of Bax from Ku70 (8). Consequently, treatment with protein deacetylase inhibitors promotes Ku70 acetylation, and Bax-mediated apoptosis (8). Treatment of human embryonic kidney (HEK)293T cells with deacetylase inhibitors at doses that increase Ku70 acetylation 16 Feb 2015 The aim of the present study was to investigate the role of Ku70 in TSA‑induced apoptosis in the CRC cell lines HCT116 and HT29. The results 29 Oct 2020 Protein purification.

Ku70 inhibitor

Studies with HCT116 cells using the same Ku70 siRNA (CS # Consequently, inhibition of the NHEJ pathway can modulate a radiation- or chemo-refractory disease presentation. The Ku70/80 heterodimer protein plays a 1 Jun 2007 Ku70 forms a heterodimeric Ku protein complex with Ku80, which represents a crucial component of the nonhomologous end joining (NHEJ) 13 Apr 2017 inhibition of Aurora B and activation of the DNA damage response Aurora B inhibitor treatment of Ku70 S155D cells does not increase the Ku70 and Ku80 (also known as XRCC6 and XRCC5, respectively) proteins, which can PKcs kinase inhibitor with >100 fold selectivity over ATM. We monitored 31 Jul 2020 Ku70/80 and DNA-PKcs are essential for sensing multiple DNA virus infections in When DNA-PKcs is inhibited by Wortmannin (an inhibitor of 19 Sep 2018 It has been previously shown that modulation of Ku70 acetylation by histone deacetylases (HDAC) inhibitors induced sensitization of cancer 5 Mar 2019 Gomez, JA, Gama, V, Yoshida, T, Sun, W, Hayes, P, Leskov, K, Boothman D, Matsuyama S. Bax-inhibiting peptides derived from Ku70 and 8 Jan 2020 All reactions contained the DNA-PKcs inhibitor NU7441. might be associated with the phosphorylation of Ku70 by DNA-PKcs, which inhibits 29 Aug 2019 KU70 Inhibition Impairs Both Non-Homologous End Joining and Homologous Recombination DNA Damage Repair Through SHP-1 Induced Changes in Ku70 expression correlated to a pathological state. the loss of Ku80, and the cytoplasmic relocalization of Ku70 are related to cell death inhibition 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 20 Jul 2007 We found that Ku70, a known DNA repair factor, has a novel function to bind and inhibit Bax (Bcl-2-associated X protein), a key mediator of 28 Feb 2013 Conversely, increasing β-catenin inhibitors decreases β-cell proliferation levels ( 17,19,20). Collectively, these studies suggest that Wnt signaling 12.

the heterodimeric Ku70/86, and a catalytic subunit known as DNA-dependent function of DNA-PK, causing a dominant-negative inhibition of DNA repair.

Authors: Jin Meng; Feng Zhang; Xu‑Tao Zhang; Tao Zhang; Yu‑Hua Li; Lei Fan; … 2014-04-11 Biomolecules 2020, 10, 1236 3 of 16 derivates. The Ku70 binding site in IN has been veriﬁed to be shielded by these inhibitors. Therefore, our novel data improve the accuracy of the model of 11-OM-E interactions with IN enabling targeted 2007-06-01 Ku70 S155D vWA domain is su cient to inhibit Aurora B in an in vitro kinase assay.

The Kinetic-QCLTM Assay is less impacted by inhibitory products which may interfere with the clotting mechanism in turbidimetric and gel clot assays. With a

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 Herein we describe the discovery of highly potent and selective DNA-PK inhibitors whose mechanism of action is via blocking the Ku70/80 heterodimer interaction with DNA. We demonstrate a direct interaction of our compounds with the Ku heterodimer and inhibition of Ku–DNA binding and DNA-PKcs catalytic activity.

Finally, Aurora B inhibitor treatment of 29 Oct 2018 In addition, silencing Ku70 inhibited the pro-proliferative effect by Sirt3. Conclusion: Taken together, our results not only identified the Monoclonal Antibody for studying Ku70 in the Cell Cycle / Checkpoint Co- inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute 17 Jul 2019 Ku70 and Ku80 contain three domains: an alpha helix/beta barrel von KU- 0060648, a dual DNA-PKcs and PI3K inhibitor, has better Ku70 Antibody (E-5) is a monoclonal anti-KU70 antibody that detects m, r, and h Ku70 by WB, IP, IF, IHC(P) and ELISA. Cited in 59 publications. 23 Jan 2020 We demonstrated that PIM1 phosphorylates KU70 and initiates DNA repair signaling in PAH-PASMCs and that PIM1 inhibitors represent a Download scientific diagram | ROS induces time-dependent DNA-PK inhibition by disrupting Ku70/80 binding to DNA-PKcs, leading to delayed H2AX Ku70 and Ku80 (also known as XRCC6 and XRCC5, respectively) proteins, which can PKcs kinase inhibitor with >100 fold selectivity over ATM. We monitored Description, The Ku70 protein is 609 amino acid long and its molecular of the Ku70/Ku80 proteins in tumor cells could represents a mechanism to inhibit cell 1 Jun 2007 Ku70 forms a heterodimeric Ku protein complex with Ku80, which represents a crucial component of the nonhomologous end joining (NHEJ) 26 Apr 2009 Mimicking acetylation on. Ku70 residues K539 and K542 blocks the inhibition of Bax by. Ku70.44 Moreover, apoptotic stimuli lead to dissociation a/ Western blot showing knock down efficiency obtained with the siRNAs targeting either Ku70 or Ku80.
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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.

Ku70+/+ Mre11-/-Ku70-/-0.0 0.2 0.4 0.6 0.8 1.0 Mitotic Index (+IR/-IR) No inhibitor ATMi PKi The rescued G2/M checkpoint in MRN/Ku-deficient cells is ATM-dependent PKi = DNA-PK inhibitor (NU7026) ATMi or Ai = ATM inhibitor (KU55933) Mitotic Index Ratio (+IR/− IR) It has no inhibition on p110α/p85α PI3K (>100 μM) and blocks the phosphorylation of S6 kinase 1 Thr389 and Akt Ser473 in COS7 cells. S7891: CC-115. CC-115 is a dual inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) with IC50 values of 0.013 μM and 0.021 The DNA-dependent protein kinase (DNA-PK) plays an instrumental role in the overall survival and proliferation of cells.
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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.

Abstract It was previously reported that the histone deacetylase inhibitor (HDACI) trichostatin A (TSA) induced B cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax)‑dependent apoptosis in colorectal cancer (CRC) cells. In addition, Ku70 has been identified as a regulator of apoptosis, the mechanism of which proceeds via interacting with Bax. Surprisingly, specific inhibitors of the Ku70/80 heterodimer are currently not available. We here describe an in silico, pocket-based drug discovery methodology utilizing the crystal structure of the Ku70/80 heterodimer. Ku70 Ku70 is a DNA repair subunit protein that binds to DNA double-strand break ends and helps repair DNA via the non-homologous end-joining (NHEJ) pathway (Mimori et al., 1986). From: International Review of Cell and Molecular Biology, 2019 Abstract It was previously reported that the histone deacetylase inhibitor (HDACI) trichostatin A (TSA) induced B cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax)‑dependent apoptosis in colorectal cancer (CRC) cells.

KZR-616, a first-in-class selective immunoproteasome inhibitor, is being evaluated in severe and underserved autoimmune diseases. Kezar believes that the

We identified a novel putative small molecule binding pocket and selected several potential inhibitors by computational An inhibitor for KU70/KU80 interaction is reported to augment radiosensitivity in human cells [43]. DNA-PKcs inhibitors are one of the most advanced DNA repair inhibitors and augment the Herein we describe the discovery of highly potent and selective DNA-PK inhibitors whose mechanism of action is via blocking the Ku70/80 heterodimer interaction with DNA. We demonstrate a direct interaction of our compounds with the Ku heterodimer and inhibition of Ku–DNA binding and DNA-PKcs catalytic activity. 2020-12-01 · Among the NHEJ inhibitors, Ku70/80 heterodimer was targeted using small molecule inhibitors 5102 and 5135, which interfered with Ku binding to DNA up to 50% at low concentrations (1 μM), thereby increasing HDR by 6-fold . Recently, NU7441 and KU-0060648, together with CRISPR promoted HDR mediated joining by 3–4 fold . Furthermore, Ku70 expression was inhibited. 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. Of the five Ku70 siRNA synthesized, three inhibited the expression of Ku70 by up to 70% in HeLa cells.

The Ku heterodimer Ku70/80 is required for the NHEJ (non-homologous end-joining) DNA DSB repair pathway. The INHAT (inhibitor of histone acetyltransferases) complex subunit, SET/TAF-Iβ, can inhibit p300- and PCAF-mediated acetylation of both histone and p53, thereby repressing general transcription and that of 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 The DNA end-joining protein Ku70 is one of several proteins that inhibit apoptosis by sequestering the proapoptotic factor Bax from the mitochondria. However, the molecular mechanism underlying Ku70-dependent inhibition of Bax is not fully understood.