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THE p65 SUBUNIT OF NF-κB FOR THE RADIOSENSITIZATION OF CELLS
THE p65 SUBUNIT OF NF-κB FOR THE RADIOSENSITIZATION OF CELLS
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机译:NF-κB的p65亚单位对细胞的放射增敏作用
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摘要
The transcription factor NF-κB is activated in response to various stimuli including ionizing radiation. Disruption of NF-κB activation by mutant forms of the NF-κB inhibitor IκB-α or by proteasome inhibitors enhances both sensitivity to radiation and radiation-induced apoptosis. The present invention shows that expression of a dominant negative fragment of human p65 (p65DN) leads to down-regulation of both endogenous p65 protein and its mRNA. The dominant negative protein also inhibits radiation-induced NF-κB activation by preventing the proteolysis of IκB-α, resulting in enhancement of cellular radiosensitivity and radiation-induced apoptosis. The region of p65 in the dominant negative fragment is thus a molecular target for disruption of NF-κB activation and sensitization of tumors to radiotherapy.
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