Shishkin S S, Eremina L S, Kovalev L I, Kovaleva M A
Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, 119071, Russia.
Biochemistry (Mosc). 2013 Dec;78(13):1415-30. doi: 10.1134/S000629791313004X.
This review considers the major features of human proteins AGR2 and ERp57/GRP58 and of other members of the protein disulfide isomerase (PDI) family. The ability of both AGR2 and ERp57/GRP58 to catalyze the formation of disulfide bonds in proteins is the parameter most important for assigning them to a PDI family. Moreover, these proteins and also other members of the PDI family have specific structural features (thioredoxin-like domains, special C-terminal motifs characteristic for proteins localized in the endoplasmic reticulum, etc.) that are necessary for their assignment to a PDI family. Data demonstrating the role of these two proteins in carcinogenesis are analyzed. Special attention is given to data indicating the presence of biomarker features in AGR2 and ERp57/GRP58. It is now thought that there is sufficient reason for studies of AGR2 and ERp57/GRP58 for possible use of these proteins in diagnosis of tumors. There are also prospects for studies on AGR2 and ERp57/GRP58 leading to developments in chemotherapy. Thus, we suppose that further studies on different members of the PDI family using modern postgenomic technologies will broaden current concepts about functions of these proteins, and this will be helpful for solution of urgent biomedical problems.
本综述探讨了人类蛋白质AGR2和ERp57/GRP58以及蛋白质二硫键异构酶（PDI）家族其他成员的主要特征。AGR2和ERp57/GRP58催化蛋白质中二硫键形成的能力是将它们归为PDI家族最重要的参数。此外，这些蛋白质以及PDI家族的其他成员具有特定的结构特征（硫氧还蛋白样结构域、内质网定位蛋白特有的特殊C末端基序等），这些特征是将它们归为PDI家族所必需的。分析了证明这两种蛋白质在致癌作用中作用的数据。特别关注了表明AGR2和ERp57/GRP58具有生物标志物特征的数据。目前认为，有充分理由研究AGR2和ERp57/GRP58，以便在肿瘤诊断中可能使用这些蛋白质。对AGR2和ERp57/GRP58的研究也有望推动化疗的发展。因此，我们认为，利用现代后基因组技术对PDI家族不同成员进行进一步研究将拓宽目前关于这些蛋白质功能的概念，这将有助于解决紧迫的生物医学问题。
