miRs-138 and -424 control palmitoylation-dependent CD95-mediated cell death by targeting acyl protein thioesterases 1 and 2 in CLL

摘要: Resistance toward CD95-mediated apoptosis is a hallmark of many different malignancies, as it known from primary chronic lymphocytic leukemia (CLL) cells. Previously, we could show that miR-138 and -424 are downregulated in CLL Here, identified 2 new target genes, namely acyl protein thioesterase (APT) 1 2, which under control both miRs thereby significantly overexpressed APTs the only enzymes to promote depalmitoylation. Indeed, membrane proteins less palmitoylated cells compared with normal B We directly interact CD95 depalmitoylation, thus impairing mediated through CD95. Specific inhibition by siRNAs, treatment miRs-138/-424, pharmacologic approaches restore other cancer cells, pointing an important regulatory role apoptosis. The identification depalmitoylation reaction microRNA (miRNA) provides novel molecular mechanism for how malignant escape introduce palmitoylation posttranslational modification CLL, might impact on localization, mobility, function molecules, survival signaling, migration.