Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome pathway in p53-mediated apoptosis of human cancer cells.

摘要: Apoptosis is a morphologically distinct form of programmed cell death that plays major role in cancer treatments. This cellular suicide program known to be regulated by many different signals from both intracellular and extracellular stimuli. Here we report p53 suppressed expression the FLICE-inhibitory protein (FLIP) potentially blocks apoptotic signaling human colon lines expressing mutated wild-type p53. In contrast, receptor KILLER/DR5 (TRAIL-R2) had no effect on FLIP expression, although exogenous induce expression. line with these observations, FLIP-negative cells were sensitive p53- KILLER/DR5-mediated apoptosis, whereas containing high levels underwent when triggered ectopic but not Treating specific inhibitor proteasome inhibited decrease p53, suggesting enhances degradation via ubiquitin-proteasome pathway. Thus, data indicate p53-mediated downregulation may explain potent sensitization induced gene transfer.