Small GTPase RAB45-mediated p38 activation in apoptosis of chronic myeloid leukemia progenitor cells

Posted by rob on January 9, 2012 under Uncategorized | Comments are off for this article

In this study, we found that treatment with ABL kinase inhibitors or depletion of BCR-ABL induced the expression of RAB45 messenger RNA and protein and induced apoptosis via reduction of mitochondrial membrane potential and p38 activation in CML cell lines and BCR-ABL+ progenitor cells from CML patients. Overexpressed RAB45 induced the activation of caspases-3 and -9 and reduced the expression of Survivin, XIAP, c-IAP1 and c-IAP2 in CML cells. Moreover, in colony-forming cells derived from CML-aldehyde dehydrogenasehi/CD34+ cells, treatment with ABL kinase inhibitors induced RAB45 expression and reduced mitochondrial membrane potential, resulting in inhibited colony formation of Bcr-Abl+ progenitor cells. The overexpression of RAB45 significantly decreased colony numbers and induced apopto…
More