The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells.
The transcription factor nuclear factor-kappaB (NF-kappaB) is activated in response to various stimuli including ionizing radiation. Disruption of NF-kappaB activation by mutant forms of the NF-kappaB inhibitor IkappaB-alpha or by proteasome inhibitors enhances both sensitivity to radiation and radiation-induced apoptosis. Human squamous carcinoma SCC-35 cells stably expressing a fragment (residues 1 to 84) of human p65 have been shown to exhibit down-regulation of both endogenous p65 mRNA and its protein. The mutant protein also inhibited radiation-induced NF-kappaB activation by preventing the proteolysis of IkappaB-alpha. This resulted in enhancement of cellular radiosensitivity and radiation-induced apoptosis. The NH(2)-terminal region of p65 is thus a potential molecular target for disruption of NF-kappaB activation and sensitization of tumors to radiotherapy.
Kim
Kyoung M
KM
Department of Radiation Medicine, Division of Radiation Research, Georgetown University, Research Building, Suite E211, Box 571482, Washington, DC 20057-1482, USA.
Zhang
Yin
Y
Kim
Bo-Yeon
BY
Jeong
Sook J
SJ
Lee
Sung A
SA
Kim
Gun-Do
GD
Dritschilo
Anatoly
A
Jung
Mira
M
D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051996:Transcription Factor RelA; D014162:Transfection
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011838:Radiation-Sensitizing Agents; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha