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Deconvoluting Electrophile Signaling and Stress Response Pathways
Author(s) -
Aye yimon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.558.1
Subject(s) - keap1 , reactive oxygen species , signal transduction , oxidative stress , microbiology and biotechnology , computational biology , biology , biological pathway , organelle , chemistry , biochemistry , transcription factor , gene expression , gene
In‐depth understanding of complex biological pathways hinges upon the ability to systematically perturb individual systems within each complex network. However, current experimental conditions to study impacts of reactive oxygen species/carbonyl compounds (ROS/RCC) use far above their physiological levels and are highly non‐specific. As ROS/RCC act indiscriminately, swamping the entire proteome or organelle with a reactive species unavoidably leads to off‐target effects. Specificity in signaling and stress pathways, or response is likely lost in experimental noise. This is the principal reason why so little is known about redox regulation and specific response pathways to oxidative stress. Recent development of optical probes to report levels of H2O2 in specific organelles shows motivation and appreciation toward the need to study individual effects more thoroughly. However, an approach able to perturb individual proteins within redox regulatory pathways has not been achieved. My laboratory has recently developed a biocompatible technology that permits targeted delivery of a given RCC to individual proteins at any locale in mammalian cells. ‘Keap1‐Nrf2 signaling pathway’ serves as a proof‐of‐concept in validating our new methodology that has the potential to comprehend redox regulation and electrophile sensing networks in vivo at a level of biochemical specificity currently not possible.