Nucleoskeletal components

Nuclear events in apoptosis include DNA condensation and fragmentation, redistribution of nuclear pores, disassembly of the nuclear lamina, and redistribution and proteolysis of other nuclear proteins (29). Of the nuclear proteins proteolysed in apoptosis, several appear to be involved in DNA repair processes and in maintaining the proper conformation of chromatin through interactions with the nuclear matrix. Cleavage and reorganization of these proteins may contribute to the collapse of the nucleus in apoptosis. For example, proteolysis of lamin proteins facilitates nuclear disassembly (3). Lamins are intermediate filament proteins which form a lamina underlying the inner nuclear membrane. They have been shown to stabilize the nuclear envelope and to participate in determining the organization of the interphase nucleus (30). Two subtypes of lamins can be distinguished: i.e. the A-type lamins, which comprise lamin A, lamin AA10, and lamin C; and the B-type lamins, which comprise lamin B1 and lamin B2 (31). During apoptosis, lamins are cleaved by caspase-6 at a conserved VEID (A-type lamins) or VEVD (B-type lamins) amino acid sequence (3). Several of the nucleoskeleton proteins proteolysed in apoptosis appear to be autoantigens (32). Cleavage and modification of autoantigens may reveal immunocryptic epitopes that could potentially induce autoantibody response (32).

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