TY - CHAP
T1 - Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
AU - Kensler, Thomas W.
AU - Wakabayashi, Nobunao
AU - Biswal, Shyam
PY - 2007
Y1 - 2007
N2 - Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from endogenous and exogenous stresses. The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway. These mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic consequences of acute exposures to environmental agents and drugs, inflammatory stresses, as well as chronic exposures to cigarette smoke and other carcinogens. Under quiescent conditions, the transcription factor Nrf2 interacts with the actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching interaction maintains low basal expression of Nrf2-regulated genes. However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival. This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
AB - Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from endogenous and exogenous stresses. The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway. These mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic consequences of acute exposures to environmental agents and drugs, inflammatory stresses, as well as chronic exposures to cigarette smoke and other carcinogens. Under quiescent conditions, the transcription factor Nrf2 interacts with the actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching interaction maintains low basal expression of Nrf2-regulated genes. However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival. This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
KW - Antioxidant response element
KW - Cytoprotection
KW - Gene expression
KW - Knockout mice
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=33847050801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847050801&partnerID=8YFLogxK
U2 - 10.1146/annurev.pharmtox.46.120604.141046
DO - 10.1146/annurev.pharmtox.46.120604.141046
M3 - Chapter
C2 - 16968214
AN - SCOPUS:33847050801
SN - 0824304470
SN - 9780824304478
T3 - Annual Review of Pharmacology and Toxicology
SP - 89
EP - 116
BT - Annual Review of Pharmacology and Toxicology
A2 - Cho, Arthur
ER -