WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress.
WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress.
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WDR-23 和 SKN-1/Nrf2 与 BLI-3 双氧化酶协调响应碘化物触发的氧化应激
DOI：
10.1534/g3.118.200586
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发表时间：
2018-11-06
期刊：
影响因子：
--
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Xu Z;Hu Y;Deng Y;Chen Y;Hua H;Huang S;Nie Q;Pan Q;Ma DK;Ma L
动物利用保守的机制来调节氧化应激。梭秀丽线虫SKN-1蛋白与脊椎动物Nrf（NF-E2相关因子）家族的帽环（CnC）转录因子同源，并作为异生素和氧化应激反应的核心调节因子发挥作用。含有WD 40重复序列的蛋白WDR-23是SKN-1活性的关键负调节因子。我们以前发现，过量碘化物诱导的氧化应激可以通过BLI-3/TSP-15/DOXA-1双氧化酶复合物的功能丧失来缓解。为了进一步理解这一过程的分子机制，我们筛选了能够在过量碘中存活的新突变体，并鉴定了skn-1的功能获得性突变和wdr-23的功能丧失性突变。SKN-1C亚型在皮下组织中发挥作用，影响动物对过量碘的反应，而SKN-1A亚型似乎起次要作用。WDR-23（LF）可以以不同于SKN-1（GF）的方式与BLI-3突变相互作用。转录组研究表明，过量的碘导致发育停滞在很大程度上独立于基因表达的变化，和wdr-23（lf）可能会影响一个子集的基因的表达，从SKN-1激活不同的机制。我们认为WDR-23和SKN-1与BLI-3/TSP-15/DOXA-1双氧化酶复合物协调，以响应碘引发的氧化应激。
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 SKN-1 coordinate with the BLI-3/TSP-15/DOXA-1 dual oxidase complex in response to iodide-triggered oxidative stress.
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影响因子：
56.9
作者：
BAGCHI, N;BROWN, TR;SUNDICK, RS
通讯作者：
SUNDICK, RS
影响因子：
3.7
作者：
Hasegawa K;Miwa J
通讯作者：
Miwa J
DOI：
10.12659/msm.883736
发表时间：
2013-01-14
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Dong W;Zhang H;Zhang P;Li X;He L;Wang Z;Liu Y
通讯作者：
Liu Y
影响因子：
7.7
作者：
Ewald, Collin Yves;Hourihan, John M.;Hynes, Nancy E.
通讯作者：
Hynes, Nancy E.
影响因子：
3.8
作者：
Hasegawa, Koichi;Miwa, Satsuki;Miwa, Johji
通讯作者：
Miwa, Johji