WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress

G3 : Genes - Genomes - Genetics
Zhaofa XuLong Ma

Abstract

Animals utilize conserved mechanisms to regulate oxidative stress. The C. elegans SKN-1 protein is homologous to the vertebrate Nrf (NF-E2-related factor) family of cap 'n' collar (CnC) transcription factors and functions as a core regulator of xenobiotic and oxidative stress responses. The WD40 repeat-containing protein WDR-23 is a key negative regulator of SKN-1 activity. We previously found that the oxidative stress induced by excess iodide can be relieved by loss of function in the BLI-3/TSP-15/DOXA-1 dual oxidase complex. To further understand the molecular mechanism of this process, we screened for new mutants that can survive in excess iodide and identified gain-of-function mutations in skn-1 and loss-of-function mutations in wdr-23 The SKN-1C isoform functions in the hypodermis to affect animal's response to excess iodide, while the SKN-1A isoform appears to play a minor role. wdr-23(lf) can interact with bli-3 mutations in a manner different from skn-1(gf) Transcriptome studies suggest that excess iodide causes developmental arrest largely independent of changes in gene expression, and wdr-23(lf) could affect the expression of a subset of genes by a mechanism different from SKN-1 activation. We propose that WDR-23 and ...Continue Reading

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Citations

Oct 27, 2021·Journal of Biochemistry·Nicolas John Lehrbach

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Datasets Mentioned

BETA
GSE117222

Methods Mentioned

BETA
transgenic
RNA-Seq

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