Genes, such as RFC5, DPB11, MEC1, DDC2, Mec3, RAD53, CHK1 and PDS1 DUN1 was reported to play an r The importance for the maintenance and stability were t deregulation of these genes LY2886721 in the genome h Frequently observed in cancer number of types. ATM, a protein kinase serine / threonine, functions as a signal transmitter of DNA damages caused to the machine downstream effector. In response to the induction CBD, is the protein kinase ATM an inactive monomer active dimer in a process of autophosphorylation on serine. The active ATM downstream effector hyperphosphorylates fast and activated CHK2. In addition, activates the kinase phosphorylates CHK2 its main substrates, CDC25A and Cdc25C, which in cells in the S phase or G2 / M phase or arrested.
Meanwhile, ATM and H2AX also hyperphosphorylates binding protein p53 to DNA-Sch The, which can then around individual nuclear foci at the site of shops Digte DNA, the amplification degree of the GDR Strengths k. The phosphorylated CH5424802 ALK Inhibitors H2AX, a leading ATM-dependent Ngigen response to IR, DNA-Sch The formed discrete nuclear foci and focused with 53BP1 protein, which was essential for the recruitment of various repair proteins Phosphorylated DNA, such as BRCA1, NBS1, Rad51 and TopoBP1. ATM-deficient cells exhibited no reduced hyperphosphorylation and foci formation of H2AX and 53BP1-c in dependence Dependence of IR compared to cells expressing wild-type ATM, what low efficiency of DNA repair. ATM of autosomal recessive progressive neurodegenerative disease has been appointed, ataxia-telangiectasia, which is the scientific journal PLoS ONE | Published in PloSOne first September 2011 | Volume 6 | Issue 9 | e25454 caused by mutations in the ATM.
The symptoms My clinics with the loss of ATM activity T associated neurodegeneration, extreme sensitivity of cells to radiation, are Immunschw Surface and Pr Disposition to cancer. Consistently, ATM-deficient M Mice Wachstumsst changes, Neurological changes Funktionsst, Radiosensitivity, infertility, birth defects in the maturation of T lymphocytes and Pr With increased disposition for cancer Hten concentrations of h Displayed hematopoietic malignancies Ethical, in particular. This ph Phenotypic Auspr mice Show conditions for both patients and ATM-deficient M That the pleiotropic functions of ATM kinase with various biological processes such as DNA repair, G1 / S, intra-S and G2 / M assigned points team of experts to apoptosis, initiation of translation, gene regulation and telomere maintenance.
Consistent with its function, mutations in the ATM or ATM in suppression of various cancers such as breast cancer, pancreatic cancer, myeloma, leukemia was Found chemistry and lymphoma. Therefore, the fully understand the molecular mechanisms of regulation of ATM in cancer again U much attention. Analysis Publicly available algorithms, we found that the protein kinase ATM is theoretically the target gene of miR-18a. In addition, we have shown that overexpression of miR-18a ATM expression by suppressing directly on ATM-39-UTR, which the F Ability of DNA repair of bulk products to and effectiveness of HRR and an increase Increase of cellular Ren radiosensitivity IR for the treatment.
Taken together, these results suggest that miR-18a plays a role Important in the regulation of ATM and may represent a therapeutic target for cancer and other diseases. Results miR-18a is shown in breast cancer lines and tissues of breast cancer by real-time PCR analysis that overexpressed miR-18a was clearly examined in all nine lines of breast cancer cells, where overexpression including ZR-75-1, ZR-75-30, SKBR3, T47D, MDA-MB-231, MDA-MB-435, MDA-MB-453, BT474 and BT-549, in S mammal epithelial cells compared to normal. In addition, comparative analysis revealed that miR-18a was overexpressed studied in 10 different tissue samples per annum