Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-C.S.I.C., Spain.
Centro de Investigación Príncipe Felipe, Valencia, Spain.
FEBS Lett. 2019 Jan;593(2):209-218. doi: 10.1002/1873-3468.13299. Epub 2018 Dec 7.
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.
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。