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多胺干扰蛋白质泛素化并导致细胞内氨基酸耗竭:细胞生长抑制的一种可能机制。

Polyamines interfere with protein ubiquitylation and cause depletion of intracellular amino acids: a possible mechanism for cell growth inhibition.

机构信息

Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-C.S.I.C., Spain.

Centro de Investigación Príncipe Felipe, Valencia, Spain.

出版信息

FEBS Lett. 2019 Jan;593(2):209-218. doi: 10.1002/1873-3468.13299. Epub 2018 Dec 7.

DOI:10.1002/1873-3468.13299
PMID:30447065
Abstract

Spermidine is a polyamine present in eukaryotes with essential functions in protein synthesis. At high concentrations spermidine and norspermidine inhibit growth by unknown mechanisms. Transcriptomic analysis of the effect of norspermidine on the plant Arabidopsis thaliana indicates upregulation of the response to heat stress and denatured proteins. Accordingly, these polyamines inhibit protein ubiquitylation, both in vivo (in yeast, Arabidopsis, and human Hela cells) and in vitro (with recombinant ubiquitin ligase). This interferes with protein degradation by the proteasome, a situation known to deplete cells of amino acids. Norspermidine treatment of yeast cells induces amino acid depletion, and supplementation of media with amino acids counteracts growth inhibition and cellular amino acid depletion but not inhibition of protein polyubiquitylation.

摘要

亚精胺是真核生物中存在的一种多胺,在蛋白质合成中具有重要功能。在高浓度下,亚精胺和降亚精胺通过未知机制抑制生长。亚精胺对植物拟南芥的转录组分析表明,它会上调对热应激和变性蛋白的反应。因此,这些多胺会抑制蛋白质的泛素化,无论是在体内(酵母、拟南芥和人类海拉细胞)还是在体外(使用重组泛素连接酶)。这会干扰蛋白酶体的蛋白质降解,这种情况已知会耗尽细胞中的氨基酸。用亚精胺处理酵母细胞会诱导氨基酸耗尽,而用氨基酸补充培养基可以对抗生长抑制和细胞氨基酸耗尽,但不能对抗蛋白质多泛素化的抑制。

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引用本文的文献

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A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins.系统探索揭示了亚精胺通过稳定与黑色素生成相关的蛋白质,从而具有治疗色素减退的潜力。
Sci Rep. 2022 Aug 25;12(1):14478. doi: 10.1038/s41598-022-18629-3.
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Genome-Wide Identification of Seven Polyamine Oxidase Genes in (L.) and Their Expression Patterns Under Various Abiotic Stresses.番茄中七个多胺氧化酶基因的全基因组鉴定及其在各种非生物胁迫下的表达模式
Front Plant Sci. 2020 Sep 4;11:544933. doi: 10.3389/fpls.2020.544933. eCollection 2020.
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Polyamine Catabolism in Plants: A Universal Process With Diverse Functions.
植物中的多胺分解代谢:一个具有多种功能的普遍过程。
Front Plant Sci. 2019 May 7;10:561. doi: 10.3389/fpls.2019.00561. eCollection 2019.