Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses.
Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses.
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DOI：
10.1089/ars.2017.7350
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发表时间：
2019-02-01
影响因子：
6.6
通讯作者：
Phang JM
中科院分区：
文献类型：
--
作者：
Phang JM
意义：越来越清楚的是，脯氨酸代谢在代谢重编程中发挥着重要作用，不仅在癌症中，而且在衰老、衰老和发育等相关领域也如此。尽管最初关注的是脯氨酸分解代谢，但许多实验室最近的研究强调了脯氨酸合成和脯氨酸循环的调节作用。最新进展：虽然脯氨酸脱氢酶/脯氨酸氧化酶 (PRODH/POX) 被认为是肿瘤蛋白 53 (P53) 激活的氧化还原信号来源，可启动细胞凋亡和自噬，但衰老已被添加到响应中。在生物合成方面，两个公认的癌基因，c-MYC 和磷酸肌醇 3-激酶 (PI3K)，显着上调脯氨酸合成酶；受影响的机制包括增强氧化还原循环和维持吡啶核苷酸。重编程已被证明会改变克隆发生和/或转移。关键问题：虽然 PRODH/POX 产生用于信号传导的活性氧 (ROS)，但细胞终点是可变的并且取决于代谢背景；这些反应的开关仍然未知。在合成方面，这些酶需要在各种癌症中进行更完整的表征，并且证明脯氨酸代谢物与其他途径的偶联可能需要研究蛋白质-蛋白质相互作用、膜转运蛋白和穿梭机。未来方向：脯氨酸代谢轴可以作为整合多种调节机制的支架。一旦被理解为癌症代谢的核心机制，脯氨酸代谢可能成为辅助癌症治疗的良好靶点。
Significance: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a tumor protein 53 (P53)-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses. On the biosynthetic side, two well-recognized oncogenes, c-MYC and phosphoinositide 3-kinase (PI3K), markedly upregulate enzymes of proline synthesis; mechanisms affected include augmented redox cycling and maintenance of pyridine nucleotides. The reprogramming has been shown to shift in clonogenesis and/or metastasis. Critical Issues: Although PRODH/POX generates reactive oxygen species (ROS) for signaling, the cellular endpoint is variable and dependent on metabolic context; the switches for these responses remain unknown. On the synthetic side, the enzymes require more complete characterization in various cancers, and demonstration of coupling of proline metabolites to other pathways may require studies of protein–protein interactions, membrane transporters, and shuttles. Future Directions: The proline metabolic axis can serve as a scaffold on which a variety of regulatory mechanisms are integrated. Once understood as a central mechanism in cancer metabolism, proline metabolism may be a good target for adjunctive cancer therapy.
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影响因子：
5.9
作者：
Comes, Stefania;Gagliardi, Miriam;Laprano, Nicola;Fico, Annalisa;Cimmino, Amelia;Palamidessi, Andrea;De Cesare, Dario;De Falco, Sandro;Angelini, Claudia;Scita, Giorgio;Patriarca, Eduardo J.;Matarazzo, Maria R.;Minchiotti, Gabriella
通讯作者：
Minchiotti, Gabriella
影响因子：
11.2
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
5.9
作者：
D'Aniello C;Habibi E;Cermola F;Paris D;Russo F;Fiorenzano A;Di Napoli G;Melck DJ;Cobellis G;Angelini C;Fico A;Blelloch R;Motta A;Stunnenberg HG;De Cesare D;Patriarca EJ;Minchiotti G
通讯作者：
Minchiotti G
影响因子：
9.8
作者：
FLEMING, GA;HAGEDORN, CH;PHANG, JM
通讯作者：
PHANG, JM
影响因子：
15.3
作者：
EAGLE, H;PIEZ, K
通讯作者：
PIEZ, K