Abstract
Ionizing radiation (IR) plays a key role in both areas of carcinogenesis and anticancer radiotherapy. The ATM (ataxia-telangiectasia mutated) protein, a sensor to IR and other DNA-damaging agents, activates a wide variety of effectors involved in multiple signaling pathways, cell cycle checkpoints, DNA repair and apoptosis. Accumulated evidence also indicates that the transcription factor NF-κB (nuclear factor-kappaB) plays a critical role in cellular protection against a variety of genotoxic agents including IR, and inhibition of NF-κB leads to radiosensitization in radioresistant cancer cells. NF-κB was found to be defective in cells from patients with A-T (ataxia-telangiectasia) who are highly sensitive to DNA damage induced by IR and UV lights. Cells derived from A-T individuals are hypersensitive to killing by IR. Both ATM and NF-κB deficiencies result in increased sensitivity to DNA double strand breaks. Therefore, identification of the molecular linkage between the kinase ATM and NF-κB signaling in tumor response to therapeutic IR will lead to a better understanding of cellular response to IR, and will promise novel molecular targets for therapy-associated tumor resistance. This review article focuses on recent findings related to the relationship between ATM and NF-κB in response to IR. Also, the association of ATM with the NF-κB subunit p65 in adaptive radiation response, recently observed in our lab, is also discussed.
Keywords: ATM, NF-κB, ionizing radiation
Current Cancer Drug Targets
Title: ATM-NF-κB Connection as a Target for Tumor Radiosensitization
Volume: 7 Issue: 4
Author(s): Kazi Mokim Ahmed and Jian Jian Li
Affiliation:
Keywords: ATM, NF-κB, ionizing radiation
Abstract: Ionizing radiation (IR) plays a key role in both areas of carcinogenesis and anticancer radiotherapy. The ATM (ataxia-telangiectasia mutated) protein, a sensor to IR and other DNA-damaging agents, activates a wide variety of effectors involved in multiple signaling pathways, cell cycle checkpoints, DNA repair and apoptosis. Accumulated evidence also indicates that the transcription factor NF-κB (nuclear factor-kappaB) plays a critical role in cellular protection against a variety of genotoxic agents including IR, and inhibition of NF-κB leads to radiosensitization in radioresistant cancer cells. NF-κB was found to be defective in cells from patients with A-T (ataxia-telangiectasia) who are highly sensitive to DNA damage induced by IR and UV lights. Cells derived from A-T individuals are hypersensitive to killing by IR. Both ATM and NF-κB deficiencies result in increased sensitivity to DNA double strand breaks. Therefore, identification of the molecular linkage between the kinase ATM and NF-κB signaling in tumor response to therapeutic IR will lead to a better understanding of cellular response to IR, and will promise novel molecular targets for therapy-associated tumor resistance. This review article focuses on recent findings related to the relationship between ATM and NF-κB in response to IR. Also, the association of ATM with the NF-κB subunit p65 in adaptive radiation response, recently observed in our lab, is also discussed.
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Cite this article as:
Mokim Ahmed Kazi and Jian Li Jian, ATM-NF-κB Connection as a Target for Tumor Radiosensitization, Current Cancer Drug Targets 2007; 7 (4) . https://dx.doi.org/10.2174/156800907780809769
DOI https://dx.doi.org/10.2174/156800907780809769 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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