Prasad S, Soldatenkov V A, Srinivasarao G, Dritschilo A
Department of Radiation Medicine, Division of Radiation Research, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Int J Oncol. 1999 Mar;14(3):563-70. doi: 10.3892/ijo.14.3.563.
The intermediate filament network spreading from the cell periphery to the nucleus forms dynamic linkages between nuclear matrix, actin microfilaments, and the extracellular matrix. The six different types (types I-VI) of IF proteins consisting of nearly 50 different proteins form at least nine different kinds of filaments depending on the tissue types: keratins, lamins, vimentin, desmin, neurofilaments, peripherin, alpha-internexin, glial fibrillary acidic protein and nestin. Their tissue specific expression in normal cells and differential expression/assembly in neoplasia has been of immense value in tumor diagnosis. At the same time, recent in vitro studies point out that keratins, lamins and vimentin are subject to caspase-mediated proteolysis in an apoptosis-related manner. We reviewed the experimentally demonstrated P4-P1 motif specificities of caspases in the selection of substrates in the IF protein family. In addition, we provided clues to possible cleavage of additional IF proteins during programmed cell death, based on acceptable cut site motifs indicated by searches using the PIR protein sequence database. The present review concludes with presentation of evidence on the emerging roles of IFs in association with intermediate filament associated proteins in the dynamic remodeling of the cell during development of neoplastic phenotype and execution of apoptosis.
从细胞周边延伸至细胞核的中间丝网络在核基质、肌动蛋白微丝和细胞外基质之间形成动态连接。由近50种不同蛋白质组成的六种不同类型（I型至VI型）中间丝蛋白根据组织类型形成至少九种不同的丝：角蛋白、核纤层蛋白、波形蛋白、结蛋白、神经丝、外周蛋白、α-中间连接蛋白、胶质纤维酸性蛋白和巢蛋白。它们在正常细胞中的组织特异性表达以及在肿瘤形成中的差异表达/组装在肿瘤诊断中具有巨大价值。同时，最近的体外研究指出，角蛋白、核纤层蛋白和波形蛋白以凋亡相关的方式受到半胱天冬酶介导的蛋白水解作用。我们回顾了实验证明的半胱天冬酶在中间丝蛋白家族底物选择中的P4 - P1基序特异性。此外，基于使用PIR蛋白质序列数据库搜索显示的可接受切割位点基序，我们提供了在程序性细胞死亡期间其他中间丝蛋白可能被切割的线索。本综述最后展示了关于中间丝在肿瘤表型发展和凋亡执行过程中与中间丝相关蛋白结合在细胞动态重塑中新兴作用的证据。
