Post-Translational Modification of GPX4 is a Promising Target for Treating Ferroptosis-Related Diseases.
Post-Translational Modification of GPX4 is a Promising Target for Treating Ferroptosis-Related Diseases.
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DOI：
10.3389/fmolb.2022.901565
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
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谷胱甘肽过氧化物酶4（GPX 4）是最重要的抗氧化酶之一。GPX 4作为铁凋亡的关键调节因子，在过去10年中在癌症、心血管和神经科学研究领域引起了相当大的关注。如何调控GPX4活性已成为当今研究的热点。GPX4蛋白水平由转录因子SP2或Nrf2转录调控。GPX 4活性可以通过补充细胞内硒或谷胱甘肽而上调，并且也可以被铁凋亡诱导剂如ML162和RSL3抑制。GPX 4水平/活性的这些调节机制已经在临床前研究中显示出治疗铁凋亡相关疾病的巨大潜力，特别是在癌细胞中。直到最近，研究表明GPX4可以进行翻译后修饰（PTM），如泛素化，琥珀酸化，磷酸化和糖基化。GPX4的PTM影响GPX4的蛋白质水平/活性，这表明修饰这些过程可以是治疗铁中毒相关疾病的潜在疗法。本文综述了GPX4的蛋白质特性、酶学性质和PTM。这也为通过靶向GPX4的PTM治疗铁中毒相关疾病提供了一个假设的想法。
Glutathione peroxidase 4 (GPX4) is one of the most important antioxidant enzymes. As the key regulator of ferroptosis, GPX4 has attracted considerable attention in the fields of cancer, cardiovascular, and neuroscience research in the past 10 years. How to regulate GPX4 activity has become a hot topic nowadays. GPX4 protein level is regulated transcriptionally by transcription factor SP2 or Nrf2. GPX4 activity can be upregulated by supplementing intracellular selenium or glutathione, and also be inhibited by ferroptosis inducers such as ML162 and RSL3. These regulatory mechanisms of GPX4 level/activity have already shown a great potential for treating ferroptosis-related diseases in preclinical studies, especially in cancer cells. Until recently, research show that GPX4 can undergo post-translational modifications (PTMs), such as ubiquitination, succination, phosphorylation, and glycosylation. PTMs of GPX4 affect the protein level/activity of GPX4, indicating that modifying these processes can be a potential therapy for treating ferroptosis-related diseases. This article summarizes the protein characteristics, enzyme properties, and PTMs of GPX4. It also provides a hypothetical idea for treating ferroptosis-related diseases by targeting the PTMs of GPX4.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
PES1 的 SUMO 化通过抑制其泛素化来上调其稳定性和功能
影响因子：
--
作者：
Li S;Wang M;Qu X;Xu Z;Yang Y;Su Q;Wu H
通讯作者：
Wu H
影响因子：
64.8
作者：
Chen S;Zhu B;Yin C;Liu W;Han C;Chen B;Liu T;Li X;Chen X;Li C;Hu L;Zhou J;Xu ZX;Gao X;Wu X;Goding CR;Cui R
通讯作者：
Cui R
影响因子：
14.8
作者：
Dekker, Frank J.;Rocks, Oliver;Waldmann, Herbert
通讯作者：
Waldmann, Herbert
DOI：
10.1515/bchm3.1995.376.11.651
发表时间：
1995-11-01
期刊：
BIOLOGICAL CHEMISTRY HOPPE-SEYLER
影响因子：
--
作者：
MAIORINO, M;AUMANN, KD;FLOHE, L
通讯作者：
FLOHE, L