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it was noted that treatment of those cells with 17 DMAG induced a smaller molecular weight MIZ 1 protein as compared to that of MIZ 1 detected in MIZ 1 transfected cells. Moreover, shown in Fig. 8 were reproducible when different anti MIZ 1 antibodies were used. It should be noted AG-1478 that on the basis of the deduced amino acid sequence of MIZ 1, its expected molecular weight is 88 kDa. To further verify data shown in Fig. 8, we executed 2 D gel analysis using CHP134 and SKNAS treated with 17 DMAG. As shown in Fig. 17 DMAG did actually produce MIZ 1 protein in these cell lines, however the drug-induced MIZ 1 protein had a smaller molecular weight and less post translational modifications as compared to that of the cells transfected with MIZ 1. Thus far, there has been no report to show that Hsp90 inhibition results in down regulation of MYC and MYCN. In this study, we've shown that Hsp90 inhibition Mitochondrion rapidly destabilizes MYCN and MYC proteins in unfavorable neuroblastoma cells. Although the exact mechanism by which Hsp90 inhibition triggers destabilization of MYC and MYCN is not clear, our claim that MYC and MYCN are on the list of Hsp90 client proteins. In addition, the AKT pathway is known to strengthen MYC and MYCN. Since treatment of neuroblastoma cells with 17 DMAG in down regulation of AKT, one could describe the destabilization of MYCN and MYC as a result of AKT inactivation. Our data also claim that there is yet an additional mechanism for MYCN and MYC destabilization in neuroblastoma cells having an intact p53 pathway. canagliflozin Inhibition of Hsp90 by 17 DMAG up regulates p53 expression and concomitantly destabilizes MYCN and MYC, as described. There is an inverse correlation between p53 expression and MYCN or MYC expression in 17 DMAG treated cell lines. This observation is in keeping with our previous study, which suggests that an increased p53 expression in a decreased MYCN expression in MYCN amplified neuroblastoma cells. Nevertheless, the identification of p53 targets that mediate the destabilization of MYCN and MYC in the neuroblastoma cells remains to be identified. Based on the data shown in Figs. 3 and 4, the induction of p21WAF1 is p53 independent and likely p53 dependent. It's unclear why CHP134 with the unchanged p53 route, fails to induce expression in response to p53 induction mediated by Hsp90 inhibition. However, depending on our experience, it is more difficult to induce p21WAF1 protein expression in CHP134 by prescription drugs as compared to other cell lines. Ergo, the p21WAF1 response system to different environmental cues might be impaired in cells. Hsp90 is famous to be crucial to the stability and function of many proteins which are important to survival and growth of cancer cells. To this end, our study shows that Hsp90 inhibition also causes HDAC6 destabilization. It is known that HDAC6 is one of the tubulin deacetylases, and ergo, HDAC6 depletion by Hsp90 inhibition in hyper acetylation of tubulin.