Inositol polyphosphate multikinase modulates redox signaling through nuclear factor erythroid 2-related factor 2 and glutathione metabolism.
Inositol polyphosphate multikinase modulates redox signaling through nuclear factor erythroid 2-related factor 2 and glutathione metabolism.
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DOI：
10.1016/j.isci.2023.107199
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发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Paul, Bindu D.
中科院分区：
文献类型：
--
作者：
Tyagi, Richa;Chakraborty, Suwarna;Tripathi, Sunil Jamuna;Jung, Ik-Rak;Kim, Sangwon F.;Snyder, Solomon H.;Paul, Bindu D.
氧化还原平衡的维持在过多的信号传导过程中起着核心作用。虽然活性氧和氮的生理水平对某些信号通路的功能至关重要，但自由基和氧化剂的过度产生会损害细胞成分。核因子红细胞2相关因子2（Nrf 2）信号级联是介导细胞对氧化应激反应的关键途径。它在多个水平上受到控制，这有助于维持细胞内的氧化还原稳态。我们在这里表明，肌醇多磷酸多激酶（IPMK）是一种Nrf 2信号转导的调节剂。IPMK结合Nrf 2并减弱Nrf 2靶基因的活化和表达。此外，IPMK的消耗导致谷胱甘肽和半胱氨酸水平升高，导致对氧化剂的抗性增加。因此，靶向IPMK可以在半胱氨酸和谷胱甘肽不足的条件下恢复氧化还原平衡。IPMK的耗尽赋予对氧化应激的抗性IPMK抑制Nrf 2，氧化应激反应的主要调节剂IPMK抑制Nrf 2信号传导，而不依赖于其催化活性。这项研究揭示了IPMK在调节细胞氧化还原稳态中的新作用生物科学;细胞生物学;分子生物学
Maintenance of redox balance plays central roles in a plethora of signaling processes. Although physiological levels of reactive oxygen and nitrogen species are crucial for functioning of certain signaling pathways, excessive production of free radicals and oxidants can damage cell components. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling cascade is the key pathway that mediates cellular response to oxidative stress. It is controlled at multiple levels, which serve to maintain redox homeostasis within cells. We show here that inositol polyphosphate multikinase (IPMK) is a modulator of Nrf2 signaling. IPMK binds Nrf2 and attenuates activation and expression of Nrf2 target genes. Furthermore, depletion of IPMK leads to elevated glutathione and cysteine levels, resulting in increased resistance to oxidants. Accordingly, targeting IPMK may restore redox balance under conditions of cysteine and glutathione insufficiency. Depletion of IPMK confers resistance to oxidative stress IPMK inhibits Nrf2, the master regulator of oxidative stress response IPMK represses Nrf2 signaling independent of its catalytic activity This study uncovers a new role for IPMK in modulating redox homeostasis in cells Biological sciences; Cell biology; Molecular biology
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影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
6.6
作者：
Deponte M
通讯作者：
Deponte M
DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
DOI：
10.1073/pnas.2100050118
发表时间：
2021-11-09
影响因子：
11.1
作者：
Erdélyi K;Ditrói T;Johansson HJ;Czikora Á;Balog N;Silwal-Pandit L;Ida T;Olasz J;Hajdú D;Mátrai Z;Csuka O;Uchida K;Tóvári J;Engebraten O;Akaike T;Børresen Dale AL;Kásler M;Lehtiö J;Nagy P
通讯作者：
Nagy P