Opposite Roles of FAP-1 and Dynamin in the Regulation of Fas (CD95) Translocation to the Cell Surface and Susceptibility to Fas Ligand-mediated Apoptosis

摘要: Human melanoma is the most aggressive form of skin cancer and extremely resistant to radiation chemotherapy. One critical parameters this resistance down-regulation Fas (CD95) cell-surface expression. Using TIG3 normal human fibroblasts cell lines, we investigated transcriptional regulation FAP-1, a regulator translocation in cell. Protein-tyrosine phosphatase FAP-1 (PTPN13, PTP-BAS) interacts with protein prevents its export from cytoplasm surface. In contrast, dynamin-2 facilitates Golgi apparatus via trans-Golgi network Suppression dynamin functions by dominant negative K44A blocks export, whereas expression specific RNA interference restores (a phenomenon that could still be down-regulated presence dominant-negative dynamin). Based on FAP-1- dynamin-dependent translocation, have created lines different levels surface Fas. Treatment these soluble ligand resulted programmed death was proportional pre-existing Taking into consideration well known observations often up-regulated metastatic tumors, established causal connection between high basal NF-κB transcription factor activity (which hallmark many types tumors) NF-κB-dependent gene finally restricts trafficking, thereby, facilitating survival cells.