Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin, Ireland.
Immunol Rev. 2010 May;235(1):105-16. doi: 10.1111/j.0105-2896.2010.00908.x.
The caspase family of cysteine proteases becomes activated in response to diverse cellular insults and coordinates apoptosis through proteolysis of hundreds of cellular substrates. Cytotoxic lymphocytes are adept at promoting apoptosis of virally infected or transformed cells through delivery of cytotoxic enzymes, such as granzyme B, into target cells via the granule exocytosis pathway. Granzyme B promotes apoptosis of target cells through direct processing of certain caspases, which leads to their autoactivation. Granzyme B can also activate caspases indirectly through proteolysis of Bid, a protein that promotes mitochondrial permeabilization and consequent activation of the apoptosome pathway to caspase activation. Evidence also indicates that granzyme B may contribute to antiviral immunity by directly suppressing viral replication through direct proteolysis of viral proteins that are essential for pathogenicity. Recent reports also suggest that granzyme B may have additional non-cytotoxic roles under certain circumstances and may also function in the extracellular space. Here, we discuss the cytotoxic and putative non-cytotoxic functions of granzyme B within the immune system.
半胱氨酸蛋白酶家族的胱天蛋白酶在响应各种细胞损伤时被激活，并通过对数百种细胞底物的蛋白水解来协调细胞凋亡。细胞毒性淋巴细胞通过细胞毒性酶（如颗粒酶 B）通过颗粒外排途径递送至靶细胞，从而擅长促进病毒感染或转化细胞的凋亡。颗粒酶 B 通过直接处理某些半胱天冬酶来促进靶细胞凋亡，这导致它们的自我激活。颗粒酶 B 还可以通过水解Bid 间接激活半胱天冬酶，Bid 是一种促进线粒体通透性和随后激活凋亡体途径以激活半胱天冬酶的蛋白。有证据表明，颗粒酶 B 还可以通过直接水解对致病性至关重要的病毒蛋白来直接抑制病毒复制，从而有助于抗病毒免疫。最近的报告还表明，颗粒酶 B 在某些情况下可能具有额外的非细胞毒性作用，并且也可能在细胞外空间发挥作用。在这里，我们讨论了颗粒酶 B 在免疫系统中的细胞毒性和潜在的非细胞毒性作用。
