Department for Molecular Biomedical Research, VIB, B-9052 Ghent, Belgium.
Trends Biotechnol. 2009 Dec;27(12):680-8. doi: 10.1016/j.tibtech.2009.09.007. Epub 2009 Oct 29.
Caspases are key players in various cellular processes, such as apoptosis, proliferation and differentiation, and in pathological conditions including cancer and inflammation. Although caspases preferentially cleave C-terminal of aspartic acid residues, their action is restricted generally to one or a few sites per protein substrate. Caspase-specific substrate recognition appears to be determined by the substrate sequences adjacent to the scissile bond. Knowledge of these substrates and the generated fragments is crucial for a thorough understanding of the functional implications of caspase-mediated proteolysis. In addition, insight into the cleavage specificity might assist in designing inhibitors that target disease-related caspase activities. Here, we critically review recently published procedures used to generate a proteome-wide view of caspase substrates.
半胱天冬酶是细胞凋亡、增殖和分化等多种细胞过程以及癌症和炎症等病理条件中的关键参与者。尽管半胱天冬酶优先切割天冬氨酸残基的 C 末端，但它们的作用通常仅限于每个蛋白质底物的一个或几个位点。半胱天冬酶特异性底物识别似乎由靠近切割键的底物序列决定。对半胱天冬酶介导的蛋白水解的功能影响的透彻理解，这些底物和生成的片段的知识是至关重要的。此外，对半胱天冬酶切割特异性的深入了解可能有助于设计针对与疾病相关的半胱天冬酶活性的抑制剂。在这里，我们批判性地回顾了最近发表的用于生成半胱天冬酶底物全蛋白质组视图的程序。
