Belviso Stefania, Iuliano Rodolfo, Amato Rosario, Perrotti Nicola, Menniti Miranda
Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Department of Human Health, University Magna Graecia of Catanzaro, Catanzaro, Italy.
PLoS One. 2017 May 24;12(5):e0178174. doi: 10.1371/journal.pone.0178174. eCollection 2017.
The human protein ASPG is an enzyme with a putative antitumor activity. We generated in bacteria and then purified a recombinant GST-ASPG protein that we used to characterize the biochemical and cytotoxic properties of the human ASPG. We demonstrated that ASPG possesses asparaginase and PAF acetylhydrolase activities that depend on a critical threonine residue at position 19. Consistently, ASPG but not its T19A mutant showed cytotoxic activity in K562, NALM-6 and MOLT-4 leukemic cell lines but not in normal cells. Regarding the mechanism of action of ASPG, it was able to induce a significant apoptotic death in K562 cells. Taken together our data suggest that ASPG, combining different enzymatic activities, should be considered a promising anti-cancer agent for inhibiting the growth of leukemia cells.
人类蛋白质ASPG是一种具有假定抗肿瘤活性的酶。我们在细菌中生成并纯化了重组GST-ASPG蛋白，用于表征人类ASPG的生化和细胞毒性特性。我们证明ASPG具有天冬酰胺酶和PAF乙酰水解酶活性，这些活性依赖于第19位的关键苏氨酸残基。一致的是，ASPG而非其T19A突变体在K562、NALM-6和MOLT-4白血病细胞系中显示出细胞毒性活性，但在正常细胞中未显示。关于ASPG的作用机制，它能够在K562细胞中诱导显著的凋亡死亡。综合我们的数据表明，结合不同酶活性的ASPG应被视为一种有前景的抗癌剂，可用于抑制白血病细胞的生长。
