Intermediate filament proteins during carcinogenesis and apoptosis (Review)

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.