BasicMechanismsofSUMOylation

Like ubiquitin, SUMO (small ubiquitin-related modifier) proteins are small protein tags that are conjugated to proteins to modify their function. The ubiquitin system tags proteins for degradation by the proteosome (see Proteosome pathway) but SUMO conjugation has a range of other functions, stabilizing some proteins and altering their subcellular localization. Sumoylation may also influence ubiquitination and protein stability indirectly. Three different SUMO proteins are conjugated to proteins, SUMO-1, SUMO-2 and SUMO-3. The SUMO-2 and SUMO-3 genes are closely related, with 86% sequence identity while SUMO-1 is less closely related with about 50% sequence identity with SUMO-2 and SUMO-3. These SUMO proteins also have distinct functions, with SUMO-1 conjugated to proteins as a monomer, while SUMO-2 and SUMO-3 are conjugated to proteins as higher molecular weight polymers with SUMO-1 terminating further SUMO addition. SUMO proteins are first activated by adenylation by one enzyme complex (SAE1/SAE2), then transferred to Ubc-9 and finally to the terminal amino group of a lysine side chain in target proteins. The same conjugation system appears to work for all three SUMO proteins.One target of SUMO modification is proteins involved in formation of the PML nuclear bodies, promoting the stability of these structures and perhaps altering their role in transcriptional regulation, cellular proliferation and anti-viral responses. Other targets of SUMO addition include DAXX, p53 and ran-Gap. The transcriptional activation by p53 is increased by SUMO addition. The localization of DAXX to the PML nuclear bodies and the localization of ran-Gap to the nuclear pores are also regulated by SUMO addition. The activity of several transcription factors is altered by sumoylation, including C/EBP proteins, c-Myb, glucocorticoid receptor, androgen receptor, and progesterone receptor. PIAS is a protein that modulates the activity of many different transcription factors perhaps by acting itself as a sumo ligase. Sumoylation of topoisomerase I alters its localization in the nucleus, and histone deacetylase enzymes are targets of this system. Viral proteins are targets of sumoylation, suggesting that infection and anti-viral cellular defenses may be affected by this system. Sumoylation may also alter the stability of proteins with polyglutamine repeats involved in neurodegenerative disorders, adding further to the important and diverse roles of this protein modification system.

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REFERENCES: Tatham MH, The Journal of Biological Chemistry (2001) 276(38): 35368-35374. Polymeric Chains of SUMO-2 and SUMO-3 are Conjugated to Protein Substrates by SAE1/SAE2 and Ubc9.