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FEBS Lett. 2011 Jul 21;585(14):2144-50. doi: 10.1016/j.febslet.2011.05.034. Epub 2011 May 27.

TRADD is critical for resistance to TRAIL-induced cell death through NF-κB activation.

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Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.


One major obstacle in the clinical application of TRAIL as a cancer therapeutic agent is the acquisition of TRAIL resistance. We found that deficiency of TRADD sensitizes cells to TRAIL-induced apoptosis. Enhanced cell death in TRADD(-/-) MEFs is associated with defective NF-κB activation, indicating that the pro-survival function of TRADD in TRAIL signaling is mediated at least in part via NF-κB activation. Moreover, siRNA knock-down of TRADD in cancer cells sensitizes them to TRAIL-induced apoptosis. Thus, TRADD has a survival role in TRAIL signaling and may be one potential target for overcoming TRAIL resistance in cancer therapy.

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