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Title: The Nrf2-Keap1 pathway is activated by steroid hormone signaling to govern neuronal remodeling
Authors: Chew, Liang Yuh 
Zhang, Heng 
He, Jianzheng
Yu, Fengwei 
Keywords: antioxidant
cytoplasm-to-nucleus translocation
dendrite pruning
ecdysone signaling
Nrf2-Keap1 pathway
steroid hormone
Issue Date: 1-Aug-2021
Publisher: Elsevier B.V.
Citation: Chew, Liang Yuh, Zhang, Heng, He, Jianzheng, Yu, Fengwei (2021-08-01). The Nrf2-Keap1 pathway is activated by steroid hormone signaling to govern neuronal remodeling. Cell Reports 36 (5) : 109466. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: The evolutionarily conserved Nrf2-Keap1 pathway is a key antioxidant response pathway that protects cells/organisms against detrimental effects of oxidative stress. Impaired Nrf2 function is associated with cancer and neurodegenerative diseases in humans. However, the function of the Nrf2-Keap1 pathway in the developing nervous systems has not been established. Here we demonstrate a cell-autonomous role of the Nrf2-Keap1 pathway, composed of CncC/Nrf2, Keap1, and MafS, in governing neuronal remodeling during Drosophila metamorphosis. Nrf2-Keap1 signaling is activated downstream of the steroid hormone ecdysone. Mechanistically, the Nrf2-Keap1 pathway is activated via cytoplasmic-to-nuclear translocation of CncC in an importin- and ecdysone-signaling-dependent manner. Moreover, Nrf2-Keap1 signaling regulates dendrite pruning independent of its canonical antioxidant response pathway, acting instead through proteasomal degradation. This study reveals an epistatic link between the Nrf2-Keap1 pathway and steroid hormone signaling and demonstrates an antioxidant-independent but proteasome-dependent role of the Nrf2-Keap1 pathway in neuronal remodeling. © 2021 The Author(s)
Source Title: Cell Reports
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109466
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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