Mutagenesis Advance Access published online on October 1, 2008
Mutagenesis, doi:10.1093/mutage/gen056
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Signalling loops and linear pathways: NF-
B activation in response to genotoxic stress
Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland
The signalling loop concept was introduced in 1991 to explain activation of membrane and cytoplasmic kinases in response to DNA damage inflicted by ionizing radiation. Damage to the chromosomal DNA was thought to provide a primary signal and a secondary signal from a nucleus to cytoplasm was assumed. This scenario was confirmed although not as originally proposed. A complex of nuclear factor-
B (NF-B) essential modulator and ataxia telangiectasia-mutated kinase activated by genotoxic agents is sent to cytoplasm, prompting nuclear translocation of the active transcription factor NF-B. In parallel, linear signalling pathways are initiated in the cytoplasm, mostly by reactive oxygen species, resulting in NF-B activation and nuclear translocation. The choice of NF-B activation pathway and the extent of activation of various pathways may be influenced by the relative degree of damage inflicted by genotoxic agents in the nuclear and cytoplasmic compartments. The ultimate pattern of cellular response is determined by availability, abundance and localization of the proteins participating in the signal transduction.
* To whom correspondence should be addressed. Tel: +48 22 504 1226; Fax: +48 22 504 1341; Email: kamil.brzoska{at}ichtj.waw.pl
Received on June 16, 2008; revised on August 23, 2008; accepted on September 2, 2008.