文章：

钙蛋白酶系统和癌症

The calpain system and cancer

原文发布日期：2011-04-21

DOI: 10.1038/nrc3050

类型: Review Article

开放获取: 否

要点：

1. The calpains are a family of cysteine proteases that catalyse the controlled proteolysis of a large number of specific substrates.
2. Although the calpain family consists of more than ten members, μ-calpain and m-calpain are the most commonly described and are ubiquitously expressed.
3. Calpastatin is the endogenous inhibitor of μ-calpain and m-calpain and it has multiple isoforms and splice variants.
4. Calpain is linked to cancer and a number of other disease states, including limb-girdle muscular dystrophy type 2A (LGMD2A) and neurodegeneration.
5. Calpain activity is linked to cellular migration through the proteolysis of focal adhesion proteins, such as focal adhesion kinase and talin.
6. Calpain is linked to cell survival through the cleavage of inhibitors of nuclear factor-κB (IκB).
7. Calpain is linked to apoptosis through cleavage of BCL-2 family members, caspases and apoptosis-inducing factor.
8. Expression of calpain and calpastatin has been linked to tumour progression and response to therapies.

要点翻译：

1. 钙蛋白酶是一类半胱氨酸蛋白酶，能催化多种特定底物的受控蛋白水解。
2. 尽管钙蛋白酶家族拥有十余种成员，其中μ-钙蛋白酶和m-钙蛋白酶研究最为广泛且普遍表达。
3. 钙抑制素是μ-钙蛋白酶和m-钙蛋白酶的内源性抑制剂，具有多种亚型和剪接变体。
4. 钙蛋白酶与癌症及多种疾病状态相关，包括肢带型肌营养不良症2A型（LGMD2A）和神经退行性病变。
5. 通过水解黏着斑蛋白（如黏着斑激酶和踝蛋白），钙蛋白酶活性与细胞迁移密切相关。
6. 借助切割核因子κB抑制因子（IκB），钙蛋白酶参与细胞存活调控。
7. 通过剪切BCL-2家族成员、半胱天冬酶及凋亡诱导因子，钙蛋白酶与细胞凋亡过程相关联。
8. 钙蛋白酶及其抑制素的表达水平与肿瘤进展及治疗反应存在显著关联。

英文摘要：

The calpains are a conserved family of cysteine proteinases that catalyse the controlled proteolysis of many specific substrates. Calpain activity is implicated in several fundamental physiological processes, including cytoskeletal remodelling, cellular signalling, apoptosis and cell survival. Calpain expression is altered during tumorigenesis, and the proteolysis of numerous substrates, such as inhibitors of nuclear factor-κB (IκB), focal adhesion proteins (including, focal adhesion kinase and talin) and proto-oncogenes (for example, MYC), has been implicated in tumour pathogenesis. Recent evidence indicates that the increased expression of certain family members might influence the response to cancer therapies, providing justification for the development of novel calpain inhibitors.

摘要翻译： 

钙蛋白酶是一类保守的半胱氨酸蛋白酶家族，能够催化多种特定底物的可控蛋白水解。其活性参与多种基本生理过程，包括细胞骨架重塑、细胞信号传导、凋亡和细胞存活。在肿瘤发生过程中，钙蛋白酶的表达发生改变，且多种底物的蛋白水解作用——如核因子-κB抑制因子（IκB）、黏着斑蛋白（包括黏着斑激酶和踝蛋白）以及原癌基因（如MYC）——被认为与肿瘤发病机制相关。最新证据表明，某些家族成员表达水平的升高可能影响癌症治疗的反应，这为开发新型钙蛋白酶抑制剂提供了理论依据。

原文链接：

The calpain system and cancer