TY - JOUR
T1 - Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane
T2 - Implications of posttranslational modifications
AU - Keum, Young Sam
PY - 2011/7
Y1 - 2011/7
N2 - The chemopreventive agent sulforaphane is an isothiocyanate derived from cruciferous vegetables. Transcriptional activation of antioxidant response element (ARE)-regulated phase II detoxification and antioxidant genes through the induction of transcription factor NF-E2-related factor-2 (Nrf2) is considered as the prime mechanism of its chemopreventive action. Cellular level of Nrf2 is tightly regulated by proteolysis through Cullin3 (Cul3)/Kelch-like ECH-associated protein 1 (Keap1)-dependent polyubiquitination. Sulforaphane is an electrophile that can react with protein thiols to form thionoacyl adducts and is believed to affect the Cys residues in Keap1 protein. In addition, sulforaphane might affect the activity of a variety of intracellular kinases to phosphorylate Nrf2 proteins, which dictates the nucleocytoplasmic trafficking of Nrf2 or modulates the Nrf2 protein stability. This review is designed to briefly account for the regulatory mechanism of Nrf2 protein expression by Cul3/Keap1 E3 ligase and for the possible roles of posttranslational modifications of cellular Keap1 or Nrf2 proteins by sulforphane in the regulation of ARE-dependent gene activation.
AB - The chemopreventive agent sulforaphane is an isothiocyanate derived from cruciferous vegetables. Transcriptional activation of antioxidant response element (ARE)-regulated phase II detoxification and antioxidant genes through the induction of transcription factor NF-E2-related factor-2 (Nrf2) is considered as the prime mechanism of its chemopreventive action. Cellular level of Nrf2 is tightly regulated by proteolysis through Cullin3 (Cul3)/Kelch-like ECH-associated protein 1 (Keap1)-dependent polyubiquitination. Sulforaphane is an electrophile that can react with protein thiols to form thionoacyl adducts and is believed to affect the Cys residues in Keap1 protein. In addition, sulforaphane might affect the activity of a variety of intracellular kinases to phosphorylate Nrf2 proteins, which dictates the nucleocytoplasmic trafficking of Nrf2 or modulates the Nrf2 protein stability. This review is designed to briefly account for the regulatory mechanism of Nrf2 protein expression by Cul3/Keap1 E3 ligase and for the possible roles of posttranslational modifications of cellular Keap1 or Nrf2 proteins by sulforphane in the regulation of ARE-dependent gene activation.
KW - Antioxidant response element (ARE)
KW - Posttranslational modifications
KW - Sulforaphane
UR - http://www.scopus.com/inward/record.url?scp=79960815640&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2011.06092.x
DO - 10.1111/j.1749-6632.2011.06092.x
M3 - Article
AN - SCOPUS:79960815640
SN - 0077-8923
VL - 1229
SP - 184
EP - 189
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
IS - 1
ER -