Of the five Ku70 siRNA synthesized, three inhibited the expression of Ku70 by up to 70% in HeLa cells. We have tested the effect of chemically synthesized siRNAs for target sequence 5 (CS #5) on the response of HeLa cells 72 hours after transfection to γ radiation and etoposide, as this showed the maximum inhibition of Ku70 expression.

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-med …. DNA double-strand breaks (DSBs) can cause either cell death or genomic instability. The Ku heterodimer Ku70/80 is required for the

Current studies indicate that Ku70 is a potential target of HDAC inhibitors and plays an important role during the induction of apoptosis. 2005-12-16 · Inhibition of Endogenous Ku70 Expression Blocks R. conorii Internalization of Mammalian Cells (A) siRNA against Ku70 is able to efficiently block Ku70 expression in transfected HeLa cells as determined by immunoblot analysis of cell lysates. Actin was used as a protein loading control. Ku70 in TSA-induced apoptosis in the CRC cell lines HCT116 and HT29. Ku70 is essential for histone deacetylase inhibitor trichostatin A-induced apoptosis JIN MENG1,2*, FENG ZHANG1*, XU‑TAO ZHANG1, TAO ZHANG3, YU-HUA LI1, LEI FAN1, YANG SUN1, HE‑LONG ZHANG4 and QI‑BING MEI1 Ku70 and Ku80 make up the Ku70/80 heterodimer. They are encoded by the Xrcc5 and Xrcc6 genes, respectively, and are highly abundant in both prokaryotes and eukaryotes.

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We here describe an in silico, pocket-based drug discovery methodology utilizing the crystal structure of the Ku70/80 heterodimer. We identified a novel putative small molecule binding pocket and selected several potential inhibitors by computational screening. 2016-07-01 KU70 Inhibition Impairs Both Non-Homologous End Joining and Homologous Recombination DNA Damage Repair Through SHP-1 Induced Dephosphorylation of SIRT1 in T-Cell Acute Lymphoblastic Leukemia (T-ALL) [corrected] High-glucose treatment inhibited the expression of Ku70 and enhanced bupivacaine-induced neurotoxicity. In contrast, the overexpression of Ku70 mitigated DNA damage and apoptosis triggered by bupivacaine and high glucose. In conclusion, our data indicated that local anesthetics may aggravate nerve toxicity in a high-glucose environment. 1.

Identifiering av ett acetyleringsberoende Ku70 / FLIP-komplex som reglerar FLIP-expression och HDAC-hämmare-inducerad apoptos. Artiklar 

Schaffer A(1), Kim EC, Wu X, Zan H, Testoni L, Salamon S, Cerutti A, Casali P. Ku70 Is Expressed and Bound with Bax in NB Cells. Ku70 is known as a nuclear protein but is also identified in the cytoplasm of cells, such as HEK293T cells, where it is associated with Bax and prevents Bax activation (30).

Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer2010Ingår i: INTERNATIONAL 

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. Inhibition of Ku70 acetylation by Set/taF-Iβ a previous report found that acetylation of Ku70 by CBP and PCaF at its C-terminal linker domain disrupts Bax interaction, thereby resulting in apoptotic cell death. to better understand the mechanisms by which Ku acetylation is regulated, we hypothesized that the INhat domain of Set/ta inhibits acetylation of Ku proF-Iβ - teins by both CBP and PCaF. HDAC inhibitors induce Ku70 acetylation with repressed c-FLIP and activated Bax in cancer cells. Current studies indicate that Ku70 is a potential target of HDAC inhibitors and plays an important role during the induction of apoptosis.

Schaffer A(1), Kim EC, Wu X, Zan H, Testoni L, Salamon S, Cerutti A, Casali P. Ku70 Is Expressed and Bound with Bax in NB Cells. Ku70 is known as a nuclear protein but is also identified in the cytoplasm of cells, such as HEK293T cells, where it is associated with Bax and prevents Bax activation (30). Specifically, inhibition of HDAC activity leads to increased acetylation of Ku70, which disrupts its binding to Bax. In turn, Bax is released from Ku70, translocates to mitochondria, and triggers the release of cytochrome c and caspase-dependent apoptosis.
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Molecular form of NF-κB inhibitory protein inhibitor of kappa B. (IκB)-αor a specific IκB  Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Idelalisib (GS-1101) in Waldenström Expression of Ku70/XRCC6 in Waldenström's Macroglobulinemia. Faktum är att MS-275 ökat markant acetylering av Ku70 och signifikant ökad Betydande inhibition av p53 inhiberade kraftigt aktiveringen av Bax och  Därför kan inhibition av CBP och p300-aktivitet sensibilisera cancerceller till under NHEJ och underlättar rekryteringen av KU70 / 80-proteiner i samarbete  Ku70-Binding Protein 1. Senast uppdaterad: 2014-12-09.

Current studies indicate that Ku70 is a potential target of HDAC inhibitors and plays an important role during the induction of apoptosis. Ku70 is a key component of non-homologous end joining machinery in the DNA damage pathway and is known to regulate apoptosis by blocking Bax entry into mitochondria. Growth inhibition and apoptosis by MI-219, MI-319 was accompanied by increase in levels of p53 along with p21 (WAF1) and the proapoptotic Puma. kidney cells.
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29 Aug 2019 KU70 Inhibition Impairs Both Non-Homologous End Joining and Homologous Recombination DNA Damage Repair Through SHP-1 Induced 

First identification of a small molecule inhibitor of the Ku70/80 heterodimer. 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. First identification of a small molecule inhibitor 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 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 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.