Functional Heterogeneity of Small Ubiquitin-related Protein Modifiers SUMO-1 versus SUMO-2/3*

By H. Saitoh, J. Hinchey. Journal of Biological Chemistry, 2000

934 citations recorded by the source corpus.

Post-translational modification marked by the covalent attachment of the ubiquitin-like protein SUMO-1/SMT3C has been implicated in a wide variety of cellular processes. Recently, two cDNAs encoding proteins related to SUMO-1 have been identified in human and mouse. The functions and regulation of these proteins, known as SUMO-2/SMT3A and SUMO-3/SMT3B, remain largely uncharacterized. We describe herein quantitative and qualitative distinctions between SUMO-1 and SUMO-2/3 in vertebrate cells. Much of this was accomplished through the application of an antibody that recognizes SUMO-2 and -3, but not SUMO-1. This antibody detected multiple SUMO-2/3-modified proteins and revealed that, together, SUMO-2 and -3 constitute a greater percentage of total cellular protein modification than does SUMO-1. Intriguingly, we found that there was a large pool of free, non-conjugated SUMO-2/3 and that the conjugation of SUMO-2/3 to high molecular mass proteins was induced when the cells were subjected to protein-damaging stimuli such as acute temperature fluctuation. In addition, we demonstrated that SUMO-2/3 conjugated poorly, if at all, to a major SUMO-1 substrate, the Ran GTPase-activating protein RanGAP1. Together, these results support the concept of important distinctions between the SUMO-2/3 and SUMO-1 conjugation pathways and suggest a role for SUMO-2/3 in the cellular responses to environmental stress.

Subfields: Immunology, Molecular Biology, Parasitology

View Paper: https://www.semanticscholar.org/paper/650b97acd53ba8768bc69be1df9b3a8a1ded871f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. F. Melchior
2. P. Pandolfi
3. G. Gill
4. Annette Flotho

In Molecular Biology

1. G. Gill
2. P. Pandolfi
3. Toby J. Gibson
4. J. Seeler
5. A. Dejean
6. Francesca Diella
7. Aidan Budd
8. Claudia Chica

In Parasitology

1. F. Melchior
2. G. Gill
3. Annette Flotho

Citations in the corpus

• Arsenic degrades PML or PML–RARα through a SUMO-triggered RNF4/ubiquitin-mediated pathway (2008, background): “Several types of stress trigger increases in global SUMO conjugation level”
• Understanding eukaryotic linear motifs and their role in cell signaling and regulation. (2008, background): “RanGAP1 is preferentially modified with SUMO-1 (84), the topoisomerase II with SUMO-2 and -3 (85).”
• Nuclear and unclear functions of SUMO (2003, background): “Saitoh et al.14 showed that, in mammalian cells, the majority of SUMO1 exists in the conjugated form, whereas the SUMO2 and SUMO3 isoforms exist primarily as free proteins that are subject to rapid conjugation after cellular stress.”
• SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? (2004, background): “SUMO-1 and SUMO-2/3 appear to modify both common and different substrates.”
• The transcriptional role of PML and the nuclear body (2000, background): “Recently, two homologues of SUMO-1 — SUMO-2 and SUMO-3 — have been clone”
• Sumoylation: a regulatory protein modification in health and disease. (2013, methodology): “Although SUMO2 and -3 are very similar (97% sequence identity for human proteins) and presently cannot be distinguished by antibodies, SUMO1 is quite divergent (47% sequence identity between mature human SUMO1 and SUMO2).”