Ubiquitin-related modifier

Since the discovery of ubiquitin as a polypeptide modifier of substrate proteins, several other proteins related to ubiquitin have been discovered (Table 3). Some of the proteins such as small ubiquitin-related modifier (SUMO) and Rubl are conjugated to substrate proteins in a manner similar to conjugation of ubiquitin. It is not clear whether this process is generally applicable to all UbL proteins. SUMO and Rubl have been investigated in some detail and the findings are described below. 

Lee GW, Melchior F, Matunis MJ, Mahajan R, Tian Q, Anderson P (1998) Modification of Ran GTPase-activating protein by the small ubiquitin-related modifier SUMO-1 requires Ubc9, an E2-type ubiquitin-conjugating enzyme homologue. J Biol Chem 273 6503-6507... 

Small nbiqnitinlike (UBL) modifier small ubiquitin-related modifier sentrin A chaperone protein Simian vims 40 Seminal vesicle secretion... 

In the nucleus, SREBPs activity is directly and indirectly controlled by post-translational modification (Eberle et al., 2004). SREBPs are modified by the small ubiquitin-related modifier (SUMO)-l. Sumoylation of SREBPs represses the activity of the transcription factor without modifying its degradation (Hirano et al., 2003). 

Bayer, P., Arndt, A., Metzger, S., Mahajan, R., Melchior, F., Jaenicke, R., and Becker, J. (1998). Structure determination of the small ubiquitin-related modifier SUMO-1. J. Mol Biol 280, 275-286. 

Schwartz, D. C. and Hochstrasser, M. A superfamily of protein tags ubiquitin, SUMO and related modifiers. Trends Biochem Sci 2003, 28, 321-328. 

Small tfbiquitin-like modifier represents a family of evolutionary conserved proteins that are distantly related in amino-acid sequence to ubiquitin, but share the same structural folding with ubiquitin proteins. SUMO proteins are covalently conjugated to protein substrates by an isopeptide bond through their carboxyl termini. SUMO addition to lysine residues of target proteins, termed SUMOylation, mediates post-transla-tional modification and requires a set of enzymes that are distinct from those that act on ubiquitin. SUMOylation regulates the activity of a variety of tar get proteins including transcription factors. 

Common posttranslational modifications of proteins. Frequently modified amino adds for each moiety are described. Most modifications involve low-mass substituents (<500amu), but some modifications are small polypeptides of considerable mass such as ubiquitin or highly related peptide isomers like SUMO-1, SUMO-2, and SUMO 3. SUMO is the abbreviation for similar to ubiquitin methyl organizer , SUMO has different family members (SUMO 1, 2, and 3 that can combine with proteins). 

Sumoylation is a covalent modification of proteins that is related to, but functionally distinct from ubiquitination (review Wilson and Rangasami, 2001). As in ubiquitinylation, sumoylation involves the covalent attachment of a small protein moiety, termed SUMO, to target proteins. The reactions leading to sumoylation of substrate proteins are related to those involved in ubiquitination. El- and E2 like enzymes are responsible for the attachment of the SUMO moiety to lysine residues of the target protein. As compared to ubiquitination, sumolyation is more sequence specific and requires a particular amino acids in the neighbourhood of the lysine to be modified. 

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