THE p65 SUBUNIT OF NF-κB FOR THE RADIOSENSITIZATION OF CELLS

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-alpha 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-alpha, 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.