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GADD45 Pathway

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Genotoxic stress is an important and ubiquitous type of stress that cells are inevitably exposed to over the life span of an organism. Many potentially damaging agents both from the environment and from endogenous processes involving activated oxygen species and other reactive agents can damage the DNA in cells (Ref.1). GADD45 induction by BRCA1 leads to programmed cell death through the JNK pathway via interaction with the upstream kinase MTK1/MEKK4. JNK has been shown to be involved in the induction of apoptosis after genotoxic stress and UV radiation. However, JNK and p38 may exert antagonistic effects depending on cell context, cross-talk with other signaling pathways and intensity and duration of the stimulus. Originally, JNK activation and inhibition experiments indicated a [...]


1.The involvement of WT1 in the regulation of GADD45a in response to genotoxic stress.
Johnson D, Hastwell PW, Walmsley RM.
Mutagenesis. 2013 Jul;28(4):393-9. doi: 10.1093/mutage/get015. Epub 2013 Mar 9.
2.GADD45 proteins: central players in tumorigenesis.
Tamura RE, de Vasconcellos JF, Sarkar D, Libermann TA, Fisher PB, Zerbini LF.
Curr Mol Med. 2012 Jun;12(5):634-51. Review.
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