Department of Experimental Medical Science, Lund University, Lund, Sweden.
Essays Biochem. 2009 Nov 4;46:11-24. doi: 10.1042/bse0460002.
The polyamines are essential for a variety of functions in the mammalian cell. Although their specific effects have not been fully elucidated, it is clear that the cellular polyamines have to be kept within certain levels for normal cell function. Polyamine homoeostasis in mammalian cells is achieved by a complex network of regulatory mechanisms affecting synthesis and degradation, as well as membrane transport of polyamines. The two key enzymes in the polyamine biosynthetic pathway, ODC (ornithine decarboxylase) and AdoMetDC (S-adenosylmethionine decarboxylase), are strongly regulated by feedback mechanisms at several levels, including transcriptional, translational and post-translational. Some of these mechanisms have been shown to be truly unique and include upstream reading frames and ribosomal frameshifting, as well as ubiquitin-independent proteasomal degradation. SSAT (spermidine/spermine N1-acetyltransferase), which is a crucial enzyme for degradation and efflux of polyamines, is also highly regulated by polyamines. A cellular excess of polyamines rapidly induces SSAT, resulting in increased degradation/efflux of the polyamines. The polyamines appear to induce both transcription and translation of the SSAT mRNA. However, the major part of the polyamine-induced increase in SSAT is caused by a marked stabilization of the enzyme against degradation by the 26S proteasome. In addition, active transport of extracellular polyamines into the cell contributes to cellular polyamine homoeostasis. Depletion of cellular polyamines rapidly induces an increased uptake of exogenous polyamines, whereas an excess of polyamines down-regulates the polyamine transporter(s). However, the protein(s) involved in polyamine transport and the exact mechanisms by which the polyamines regulate the transporter(s) are not yet known.
多胺对于哺乳动物细胞的各种功能至关重要。尽管它们的具体作用尚未完全阐明，但显然细胞内的多胺必须保持在一定水平才能维持正常的细胞功能。哺乳动物细胞中的多胺稳态是通过影响合成和降解以及多胺膜转运的复杂调节机制网络来实现的。多胺生物合成途径中的两个关键酶，ODC（鸟氨酸脱羧酶）和 AdoMetDC（S-腺苷甲硫氨酸脱羧酶），在多个水平上受到反馈机制的强烈调节，包括转录、翻译和翻译后。其中一些机制已被证明是真正独特的，包括上游阅读框和核糖体移码以及非泛素依赖性蛋白酶体降解。SSAT（精脒/精胺 N1-乙酰转移酶）是降解和排出多胺的关键酶，也受到多胺的高度调节。细胞内多胺过剩会迅速诱导 SSAT，导致多胺的降解/外排增加。多胺似乎诱导 SSAT mRNA 的转录和翻译。然而，多胺诱导的 SSAT 增加的主要部分是由于酶对 26S 蛋白酶体降解的显著稳定。此外，细胞外多胺的主动转运进入细胞有助于细胞内多胺稳态。细胞内多胺耗竭会迅速诱导外源性多胺的摄取增加，而多胺过剩会下调多胺转运蛋白。然而，参与多胺转运的蛋白质以及多胺调节转运蛋白的确切机制尚不清楚。
