کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2050894 | 1074184 | 2006 | 5 صفحه PDF | دانلود رایگان |
Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF-1α) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL-mediated protein destruction motif of HIF-1α. This design enables procaspase-3 to be regulated similarly with HIF-1α, being degraded under normoxia while stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic stress-induced endogenous caspases and thus the procaspase-3 was converted to active caspase-3 specifically under hypoxic conditions. These data demonstrated that the VHL-mediated protein destruction motif of HIF-1α endowed procaspase-3 with hypoxia-specific cytotoxicity.
Journal: FEBS Letters - Volume 580, Issue 24, 16 October 2006, Pages 5718–5722