[Ubiquitins, proteasomes, sumoylation and application today and in future for cancer and other diseases therapy II. Sumoylation and neddylation as posttranslational modifications of proteins and their ubiquitinylation and its significance]

Abstract

Posttranslational protein modifications are effective devices that cells use to control the functions of proteins. Ubiquitin-like protein modifiers (Ubls) are posttranslationally attached to proteins by enzymatic reactions that are similar to ubiquitin conjugation. SUMO (small ubiquitin-related modifier) family proteins are the most intriguing Ubls. Sumoylation is the covalent attachment of SUMO to target proteins. Neddylation is the process that conjugates the ubiquitin-like polypeptide Nedd8 to the conserved lysines of cullins. Cullin family proteins organize ubiquitin ligase complexes to target numerous cellular proteins for polyubiquitinylation and subsequent proteasomal degradation. Despite the similarities in their structure and in enzymatic reactions Ubls and ubiquitin have distinct functions. In contrast with polyubiquitinylation that targets modified proteins to proteasome degradation, the biological consequences of sumoylation include the increase of protein stability. Sumoylation also helps in the protein transport from the cytoplasm to nucleus of cells, regulates transcriptional activities of proteins and mediates the binding of the protein to other proteins. Neddylation has importance for cell cycle control, signal transmission, cell differentiation and DNA repair. Recent studies linked sumoylation and neddylation of several proteins to important diseases (neurodegenerative diseases, acute promyelocytic leukemia, type I diabetes and other disorders). The regulation of these postranslational modifications may provide new targets for therapeutic intervention in several human diseases.