Cell death by blocking transcription and replication. Some poisons produce intercalating Top2 other cellular Ren effects. Anti-Top2 targeting drugs, both isotypes and Top2 and are clinically effective against a broad spectrum SGLT of tumors, including normal myeloid leukemia Chemistry Of second-hand. Was in HL-60 cells showed that the expression of Top2, Top2 in contrast to Change the w During the cell cycle wherein the h Chsten values in the phase G2 / M observed resistance against poisons in Top2 cancer cells is often associated with decreased Top2 expression, suggesting that the harm reduction Top2-mediated DNA causes resistance. Therefore, the sensitivity to poisons Top2 the cell cycle, oncogenic signaling, Top2 levels and the activity of t influenced. Ras regulates the expression of Top2 Top2 by stimulating the promoter by MEK / ERK. However, no clear relationship between the expression or activity of t observed of genes and Top2 reaction to chemotherapy. And top2 are w Phosphorylated during the cell cycle, but is st More strongly phosphorylated w During G2 and M phases of the cell cycle. Top2 durchl Runs a variety of phosphorylation may need during the mitosis. It has been shown that casein kinase casein kinase II, I δ / ε, protein kinase C, cdc2 and ERK phosphorylate Top2. In vivo phosphorylation sites in Top2 were to Ser 29 of protein kinase C at Ser 1212, Ser 1246, Ser 1353, Ser 1360 and Ser 1392, by cdc2 and ERK at Ser 1106 designated by targeted assigned CK I δ / ε, at Ser 1337 and 1524 from Ser Polo like kinase 1, 1342 and Thr, Ser 1369, Ser 1376 and covered 1524, by CKII. The functional significance of several of these phosphorylation sites in vivo remains uncertain. However, regulates the phosphorylation of Ser 1106, the enzymatic activity of t and sensitivity to drugs, and the phosphorylation of Ser 1524 regulates the checkpoint The decatenation.
Previous work has shown that activated MEK and ERK translocation into the nucleus and in a cell cycledependent mode enabled. These results show that Top2 a potential target of nuclear Ras ERK in the modulation of chromatin reorganization events w During the mitosis and other cell cycle phases. A class of drugs that Ren with ERK st Are Ras farnesyltransferase. FTI has been reported that numerous cellular Re confinement effects, Achieve Lich induction of apoptosis and cytostatic effects. W While FTI has promising activity T with leukemia Chemistry Including Lich F Ll of complete remission, these drugs have a eingeschr Of spaces efficacy as monotherapy. However, FTI, be therapeutically useful in combination with chemotherapeutic agents, such as Top2 poisons or as maintenance therapy of acute leukemia Mie S myeloma Of. Previously it was shown that the FTI synergistically in combination with microtubule-stabilizing drugs such as paclitaxel and inhibit MDR proteins. Since many chemotherapeutic agents used to treat AML target Top2, we examined the effects of FTI P2X Receptor BMS 214 662, and dual prenyltransferase inhibitor L-778 123 in combination with idarubicin in leukemic Mix cells. The cell design and methods were antique Body, reagents and other cell lines from the German Collection of Microorganisms and Cell Cultures. MAPK 1/2, MEK 1/2, H, K, N Ras, and HRP-coupled secondary Rantik Body were from Santa Cruz Biotechnology. Top2 and Top2 Antib.