TY - JOUR
T1 - Toward clinical application of the Keap1-Nrf2 pathway
AU - Suzuki, Takafumi
AU - Motohashi, Hozumi
AU - Yamamoto, Masayuki
N1 - Funding Information:
This work was supported in part by Grants-in-Aids for Creative Scientific Research and Scientific Research from Japan Society for the Promotion of Science (JSPS), the Target Protein Program from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), the Tohoku University Global COE Program for Conquest of Signal Transduction Diseases with ‘Network Medicine’, CREST from Japan Science and Technology Agency (JST), and the NAITO foundation.
PY - 2013/6
Y1 - 2013/6
N2 - The Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of cells to chemical and/or oxidative insults by regulating the basal and inducible expression of detoxification and antioxidant enzymes, ABC transporters, and other stress response enzymes and/or proteins. Increasing attention has been focused on the roles that the Keap1-Nrf2 pathway plays in the protection of our body against drug toxicity and stress-induced diseases. Simultaneously, Nrf2 has been recognized to promote oncogenesis and resistance to chemotherapeutic drugs. Cancer cells hijack Nrf2 activity to support their malignant growth and thus Nrf2 has emerged as a therapeutic target. Translational studies of the Keap1-Nrf2 system, from mechanistic understanding to clinical applications, are now important to improve human health.
AB - The Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of cells to chemical and/or oxidative insults by regulating the basal and inducible expression of detoxification and antioxidant enzymes, ABC transporters, and other stress response enzymes and/or proteins. Increasing attention has been focused on the roles that the Keap1-Nrf2 pathway plays in the protection of our body against drug toxicity and stress-induced diseases. Simultaneously, Nrf2 has been recognized to promote oncogenesis and resistance to chemotherapeutic drugs. Cancer cells hijack Nrf2 activity to support their malignant growth and thus Nrf2 has emerged as a therapeutic target. Translational studies of the Keap1-Nrf2 system, from mechanistic understanding to clinical applications, are now important to improve human health.
KW - Cul3-based ubiquitin E3 ligase
KW - cysteine code
KW - hinge and latch model
KW - stress response
KW - two-site substrate recognition model
UR - http://www.scopus.com/inward/record.url?scp=84878572136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878572136&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2013.04.005
DO - 10.1016/j.tips.2013.04.005
M3 - Review article
C2 - 23664668
AN - SCOPUS:84878572136
SN - 0165-6147
VL - 34
SP - 340
EP - 346
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 6
ER -
