Post-translational modifications, subcellular relocation and release in apoptotic microparticles: apoptosis turns nuclear proteins into autoantigens

Abstract

Autoantibodies against particular nuclear components, such as chromatin and snRNPs, are a characteristic feature of the autoimmune disease systemic lupus erythematosus. The last decade, evidence has suggested that apoptotic cells are the main source of autoantigens in this disease. Therefore, it has been proposed that protein modifications occurring during apoptosis lead to the formation of neo-epitopes, which can break the tolerance when apoptotic cells are not properly cleared. Indeed, many lupus autoantigens are prone to apoptosis-associated post-translational modifications and/or cleavage by caspases. In addition, lupus autoantigens are relocated from the nucleus to apoptotic blebs on the cell surface of early apoptotic cells. Therefore, to understand why certain nuclear proteins become autoantigens during apoptosis, it is important to know the apoptotic processing of these proteins. This review summarizes the current knowledge of apoptotic processing of lupus autoantigens and the possible effects on their encounter with the immune system in normal and autoimmune situations.