Regulation of Ferroptosis Pathway by Ubiquitination.
Regulation of Ferroptosis Pathway by Ubiquitination.
复制标题
通过泛素化调节铁死亡途径。
DOI：
10.3389/fcell.2021.699304
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Wang X;Wang Y;Li Z;Qin J;Wang P
铁凋亡是一种铁依赖性的细胞程序性死亡，在肿瘤发生、缺血再灌注损伤和各种人类退行性疾病中起着重要作用。铁缺乏症的特征是铁和脂质代谢异常。从机制上讲，过量的催化铁能够引发脂质过氧化，然后通过芬顿反应诱导铁凋亡。通过系统XC-转运蛋白介导的胱氨酸摄取，可通过足够的谷胱甘肽（GSH）合成抑制铁凋亡的诱导。因此，通过抑制胱氨酸摄取或抑制GSH合成来诱导铁凋亡被认为是癌症治疗的新策略，而铁凋亡效应的逆转能够延迟多种疾病的进展，如心脏病、脂肪性肝炎和急性肾损伤。泛素（Ub）-蛋白酶体途径（UPP）通过将Ub分子偶联到蛋白质底物的赖氨酸残基上，随后被26 S蛋白酶体识别进行降解，从而主导了大部分细胞内蛋白质的降解。泛素化参与了多种生理和病理过程。调节泛素化系统已被证明是一种潜在的癌症治疗策略。目前，越来越多的证据表明，普遍存在的修饰参与了铁凋亡，并主导了多种类型癌症的铁凋亡易感性。本文将从泛素化调控的角度对近年来铁凋亡的研究进展进行综述。此外，我们还强调了泛素化调制的潜在影响，铁蛋白分解靶向癌症治疗的前景。
Ferroptosis is an iron-dependent form of programmed cell death, which plays crucial roles in tumorigenesis, ischemia–reperfusion injury and various human degenerative diseases. Ferroptosis is characterized by aberrant iron and lipid metabolisms. Mechanistically, excess of catalytic iron is capable of triggering lipid peroxidation followed by Fenton reaction to induce ferroptosis. The induction of ferroptosis can be inhibited by sufficient glutathione (GSH) synthesis via system Xc– transporter-mediated cystine uptake. Therefore, induction of ferroptosis by inhibition of cystine uptake or dampening of GSH synthesis has been considered as a novel strategy for cancer therapy, while reversal of ferroptotic effect is able to delay progression of diverse disorders, such as cardiopathy, steatohepatitis, and acute kidney injury. The ubiquitin (Ub)–proteasome pathway (UPP) dominates the majority of intracellular protein degradation by coupling Ub molecules to the lysine residues of protein substrate, which is subsequently recognized by the 26S proteasome for degradation. Ubiquitination is crucially involved in a variety of physiological and pathological processes. Modulation of ubiquitination system has been exhibited to be a potential strategy for cancer treatment. Currently, more and more emerged evidence has demonstrated that ubiquitous modification is involved in ferroptosis and dominates the vulnerability to ferroptosis in multiple types of cancer. In this review, we will summarize the current findings of ferroptosis surrounding the viewpoint of ubiquitination regulation. Furthermore, we also highlight the potential effect of ubiquitination modulation on the perspective of ferroptosis-targeted cancer therapy.
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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
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
48
作者：
Auslander, David;Auslander, Simon;Fussenegger, Martin
通讯作者：
Fussenegger, Martin
影响因子：
16.6
作者：
Bard JAM;Goodall EA;Greene ER;Jonsson E;Dong KC;Martin A
通讯作者：
Martin A
影响因子：
5.2
作者：
Bordini, Jessica;Morisi, Federica;Campanella, Alessandro
通讯作者：
Campanella, Alessandro