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Seminar

Donna Zhang — CBC/RBC Seminar

“The Dual Role of Nrf2 in Cancer: Modulators of thte Nrf2-Keap1-ARE Pathway as a Novel Anti-cancer T

Date:
Time:
4:00 pm – 5:00 pm
Beadle Center Room: N172
1901 Vine St
Lincoln NE 68503
Additional Info: BEAD
Contact:
Carol Hegel, (402) 472-2932, carol.hegel@unl.edu
“The Dual Role of Nrf2 in Cancer: Modulators of the Nrf2-Keap1-ARE Pathway as a Novel Anti-Cancer Therapeutics” will be presented by Donna Zhang, professor, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona.

The cellular defense response regulated by Nrf2 is crucial in maintaining cellular homeostasis. Activation of this pathway has been demonstrated to confer protection against cancer. However, dysregulation of the pathway has recently been found in many cancer types, where constitutive high levels of Nrf2 promote tumor growth and result in chemoresistance. Through detailed mechanistic investigations, Keap1 has been revealed as the primary regulator of Nrf2 by functioning as a substrate adaptor of the Keap1-Cul3-Rbx1 E3 ubiquitin ligase. Many efforts have been geared to identify small synthetic molecules or natural products that inactivate Keap1-mediated ubiquitylation of Nrf2, thus activating the Nrf2 pathway. From these efforts, many Keap1-targeting Nrf2 activators have been identified and the chemopreventive effects of these compounds have been tested in rodent models and in human clinical trials. Conversely, Nrf2 inhibitors should be developed to overcome chemoresistance in tumors expressing high levels of Nrf2. The pros and cons of these Nrf2 modulators will be discussed.

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