Feeling the heat with SUMO

SUMO (small ubiquitin-like modifier) is a posttranslational modification essential for normal function in most eukaryotic cells. The sumoylation of proteins occurs through the attachment of the SUMO group to lysine residues within the target protein or through non-covalent interactions. Noncovalent binding of SUMO to proteins containing SUMO interaction motifs enables SUMO chains to act as platforms that mediate protein-protein interactions (link is external) and downstream signalling events. It has been associated with a diverse range of cellular processes from transcription to intracellular protein localisation.

A better understanding of this small ubiquitin-like modification, by identifying which proteins are modified by SUMO and determining the exact sites of SUMO conjugation, is required, but remains experimentally challenging.

The structure of SUMO2
The structure of SUMO2

Recent work from the University of Dundee has identified a crucial role fulfilled by SUMO-2 in cell survival (link is external). Modification by SUMO-2 and SUMO chain formation can be rapidly induced by proteotoxic stress, including heat, hyperosmotic, and oxidative stress, resulting from the accumulation of unfolded or damaged proteins. Heat shock or other proteotoxic stresses that cause the accumulation of misfolded proteins promote the conjugation of SUMO-2 to nuclear proteins. By combining data from CHIP–seq and RNA-seq with previously published proteomics data, Hay and colleagues found that, following heat shock, SUMO-2 is conjugated to large protein complexes; these complexes are associated with the regulatory elements of active genes that encode regulators of gene expression and the post-transcriptional modification of RNA. SUMO-2 did not directly activate or inhibit transcription, but its conjugation was required to maintain the maximal expression of target genes. The authors propose that sumoylation is an integral component of the proteotoxic stress response that helps to maintain the integrity of transcription regulatory protein complexes.

While this new research offers important insights into the role that SUMO signalling plays in cell survival, the experimental tools necessary to study SUMO have long been lacking. Both the SUMO-1 and SUMO-2 antibodies used in this study were generated in-house. This reflects the lack of available affinity tools that specifically target the SUMO modifications, as antibodies to SUMO have historically not been thoroughly explored (link is external). Without the required affinity reagents to study this system, whether they are animal-derived antibodies or synthetic antibodies, the development of research and knowledge in this area will inevitably be slow.

Generating and validating new antibodies involves long lead times and high costs and is simply not an option for many research projects. While there is only a 7 week lead time for our custom Affimer service. Affimer reagents targeted to SUMO-1 (link is external), SUMO-2, (link is external) a pan SUMO-1/2 (link is external) and yeast SUMO (link is external) are already available in our catalogue and they have been validated for use in a number of applications, including western blotting, ELISA, ITC and co-IP, so that you can get to work immediately on discovering more amazing SUMO science.