Tumor-associated protein SPIK/TATI suppresses serine protease dependent cell apoptosis
Tumor-associated protein SPIK/TATI suppresses serine protease dependent cell apoptosis
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DOI：
10.1007/s10495-008-0193-x
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发表时间：
2008-04-01
期刊：
影响因子：
7.2
通讯作者：
Block, Timothy M.
中科院分区：
文献类型：
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作者：
Lu, Xuanyong;Lamontagne, Jason;Block, Timothy M.
丝氨酸蛋白酶依赖的细胞凋亡（SPDCA）是新近发现的一种非caspase依赖的先天性凋亡途径。它不同于传统的依赖半胱天冬酶的凋亡途径，因为丝氨酸蛋白酶，而不是半胱天冬酶，对凋亡过程至关重要。SPDCA的机制尚不清楚，需要进一步研究以确定其在维持细胞稳态和疾病发展中可能发挥的任何作用。目前有关该途径的知识仅限于一些丝氨酸蛋白酶抑制剂的抑制作用。合成药物如pefabloc、AEBSF和TPCK可以抑制培养细胞中的这种凋亡过程。然而，对细胞中可抑制SPDCA的生物活性剂知之甚少。在这里，我们表明，一种名为丝氨酸蛋白酶抑制剂Kazal（SPIK/TATI/PSTI）的细胞蛋白的过度表达会导致细胞对SPDCA的敏感性显着降低，这表明SPIK是一种抑制这种细胞凋亡途径的细胞凋亡抑制剂。先前的工作将SPIK与癌症发展联系起来，表明这一发现将有助于为进一步研究SPDCA的机制及其在癌症发展中可能发挥的作用打开大门。
Serine protease dependent cell apoptosis (SPDCA) is a recently described caspase independent innate apoptotic pathway. It differs from the traditional caspase dependent apoptotic pathway in that serine proteases, not caspases, are critical to the apoptotic process. The mechanism of SPDCA is still unclear and further investigation is needed to determine any role it may play in maintaining cellular homeostasis and development of disease. The current knowledge about this pathway is limited only to the inhibitory effects of some serine protease inhibitors. Synthetic agents such as pefabloc, AEBSF and TPCK can inhibit this apoptotic process in cultured cells. There is little known, however, about biologically active agents available in the cell which can inhibit SPDCA. Here, we show that over-expression of a cellular protein called serine protease inhibitor Kazal (SPIK/TATI/PSTI) results in a significant decrease in cell susceptibility to SPDCA, suggesting that SPIK is an apoptosis inhibitor suppressing this pathway of apoptosis. Previous work has associated SPIK and cancer development, indicating that this finding will help to open the doorway for further study on the mechanism of SPDCA and the role it may play in cancer development.