FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells.
作者： P Obexer , K Geiger , P F Ambros , B Meister , M J Ausserlechner
关键词: Cancer research 、 Gene knockdown 、 Transgene 、 Apoptosis 、 Protein kinase A 、 Programmed cell death 、 Biology 、 RNA interference 、 Cell biology 、 Transcription factor 、 Mitochondrion
摘要: Protein kinase-B (PKB) and its target, the forkhead transcription factor like 1 (FKHRL1)/FoxO3a, have been suggested as regulators of neurotrophin-mediated cell survival in neuronal cells. We analyzed human neuroblastoma cells found that FKHRL1 was phosphorylated, suggesting inactivation. To study function, we infected SH-EP NB15 with a 4OH-tamoxifen-regulated FKHRL1(A3)ERtm transgene. Activation promoted cytochrome-c release caspase-dependent apoptosis. induced TRAIL BH3-only proteins Noxa Bim, implicating both extrinsic intrinsic death pathways. However, expression dnFADD did not inhibit FKHRL1-induced death, whereas Bcl2 protected against This excluded death-receptor pathway decision is regulated by Bcl2-rheostat. Importantly, RNAi knockdown or Bim decreased apoptosis, indicating cooperate to mediate death. conclude establish connection between mitochondria, are critically involved apoptosis neuroblastoma.
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