Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
PLoS One. 2013;8(1):e54017. doi: 10.1371/journal.pone.0054017. Epub 2013 Jan 11.
Spermidine/spermine N(1)-acetyltransferase 1 (Ssat1) is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis. In addition, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis. Using cross-genomic bioinformatic analysis in 10 deuterostomes, we found that ssat1 only exists in vertebrates. Comparing with mammalian, zebrafish, an evolutionarily distant vertebrate, contains 3 homologous ssat1 genes, named ssat1a, ssat1b, and ssat1c. All zebrafish homologues could be transcribed and produce active enzymes. Despite the long history since their evolutionary diversification, some features of human SSAT1 are conserved and subfunctionalized in the zebrafish family of Ssat1 proteins. The polyamine-dependent protein synthesis was only found in Ssat1b and Ssat1c, not in Ssat1a. Further study indicated that both 5' and 3' sequences of ssat1b mediate such kind of translational regulation inside the open reading frame (ORF). The polyamine-dependent protein stabilization was only observed in Ssat1b. The last 70 residues of Ssat1b were crucial for its rapid degradation and polyamine-induced stabilization. It is worth noting that only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, were able to interact with integrin α9 and Hif-1α. Thus, Ssat1b and Ssat1c might not only be a polyamine metabolic enzyme but also simultaneously respond to polyamine levels and engage in cross-talk with other signaling pathways. Our data revealed some correlations between the sequences and functions of the zebrafish family of Ssat1 proteins, which may provide valuable information for studies of their translational regulatory mechanism, protein stability, and physiological functions.
精脒/精胺 N(1)-乙酰基转移酶 1（Ssat1）是多胺互变途径中的关键酶，可维持多胺的动态平衡。此外，哺乳动物 Ssat1 还参与许多生理和病理事件，如缺氧、细胞迁移和癌变。通过对 10 个后口动物的跨基因组生物信息学分析，我们发现 ssat1 仅存在于脊椎动物中。与哺乳动物相比，进化距离较远的斑马鱼含有 3 个同源的 ssat1 基因，分别命名为 ssat1a、ssat1b 和 ssat1c。所有斑马鱼同源物都可以转录并产生有活性的酶。尽管自进化分化以来已经有很长的历史，但人类 SSAT1 的一些特征在斑马鱼家族的 Ssat1 蛋白中被保守和亚功能化。多胺依赖性蛋白合成仅在 Ssat1b 和 Ssat1c 中发现，而不在 Ssat1a 中发现。进一步的研究表明，ssat1b 的 5'和 3'序列在开放阅读框（ORF）内介导这种翻译调控。多胺依赖性蛋白稳定性仅在 Ssat1b 中观察到。Ssat1b 的最后 70 个残基对于其快速降解和多胺诱导的稳定性至关重要。值得注意的是，只有 Ssat1b 和 Ssat1c，而不是多胺不敏感的 Ssat1a，能够与整合素 α9 和 Hif-1α 相互作用。因此，Ssat1b 和 Ssat1c 可能不仅是多胺代谢酶，还能同时响应多胺水平，并与其他信号通路进行交流。我们的数据揭示了斑马鱼家族的 Ssat1 蛋白的序列和功能之间的一些相关性，这可能为研究它们的翻译调控机制、蛋白稳定性和生理功能提供有价值的信息。
