SUMO—Nonclassical Ubiquitin

Abstract

SUMO (small ubiquitin-related modifier) is the best-characterized member of a growing family of ubiquitin-related proteins. It resembles ubiquitin in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. However, in contrast to ubiquitination-often the first step on a one-way road to protein degradation-SUMOlation does not seem to mark proteins for degradation. In fact, SUMO may even function as an antagonist of ubiquitin in the degradation of selected proteins. While most SUMO targets are still at large, available data provide compelling evidence for a role of SUMO in the regulation of protein-protein interactions and/or subcellular localization.

Body language: the function of PML nuclear bodies in apoptosis regulation

“…37,38 SUMO-1 (also termed sentrin, GMP1, SMT3C or ULP1) is a small polypeptide that is covalently attached to PML and several other PML-NB components, including Sp100, 40 Daxx, 41 p53 42,43 and CBP, 44 through an enzymatic machinery similar to that of ubiquitin modification. 45 SUMOlation requires an activating E1 SUMO-1 activating enzyme (SAE)1/SAE2 heterodimer, 46 the conjugating E2 enzyme Ubc9 47,48 and the recently identified E3 SUMO ligases. [49][50][51][52] In contrast to ubiquitination, SUMOlation usually does not lead to protein degradation but regulates protein-protein interactions, subcellular localisation and activity.…”

“…For a detailed review about the function of SUMO, we refer to some recently published reviews on this topic. 45,56,57 Several reports indicate an important function of PML and its NB residents in apoptosis regulation. As discussed below, we hypothesise that PML-NBs regulate apoptosis through different mechanisms, either by serving as transcriptional modification and activation platforms for the tumour suppressor p53, and in addition, by regulating the quality and subcellular bioavailability of apoptotic regulators.…”

“…42,43,143,144 SUMO-1 is covalently attached to specific lysine residues of its target proteins by an enzymatic machinery, which is similar to that of ubiquitin modification. 45 p53 is SUMOlated at Lys386 within its regulatory domain through a complex containing the SUMO-1 conjugating enzyme Ubc9 and the SUMO-1 ligase protein inhibitor of activated STAT (PIAS)1. 51,144 However, addressing the function of p53 SUMOlation on p53 activity led to contradictory results, reaching from increased activity, 42,43 no effect 143 to decreased transcriptional activity of p53.…”

Identification and Molecular Properties of SUMO-Binding Proteins in Arabidopsis

“…As another example, the small ubiquitin-like modifier (SUMO) resembles ubiquitin in its structure and mechanism. Activation and conjugation reactions involving SUMO have much in common with what we know about ubiqutin (Johnson, 2004;Melchior, 2000;Miura and Hasegawa, 2010).…”

Small ubiquitin-like modifying protein isopeptidase assay based on poliovirus RNA polymerase activity

“…The therapeutic value of this pathway was recently validated by the introduction and clinical success of Velcade, a proteasome inhibitor, for the treatment of refractory relapsed multiple myeloma [3]. Other ubiquitin-like proteins (UBLs) 1 have recently been shown to contribute similarly to the cellular regulation of proteins, with the most extensively characterized UBL being small ubiquitin-like modifying protein (SUMO) [4].Destruction of a targeted protein via the ubiquitin system initially involves recognition by a multienzyme system that attaches ubiquitin to the target protein. Energy is required to activate ubiquitin at its carboxy terminus.…”