Small Ubiquitin-like Modifiers (SUMOs) are a family of small, related proteins that can be enzymatically conjugated to a target protein by a post-translational modification process termed SUMOylation. SUMO-1 is a highly conserved, small ubiquitin-related modifier that has been shown to be covalently conjugated to a large variety of cellular proteins (Kamitaniet al., 1997; Mahajan et al., 1997; Matunis et al., 1996). Cloning of SUMO-1 was first described by Boddy et al. (1996). SUMO-2 and SUMO-3 share 95% sequence identity, but only 50% sequence identity to SUMO-1. SUMO-1 is conjugated to a target protein in a similar way to ubiquitin and has been implicated in multiple cellular processes, including nuclear transport, cell cycle control, oncogenesis, inflammation and response to viral infection. SUMO-1 conjugation forms an isopeptide bond between Gly97 at the C-terminus of SUMO-1 and the ε-amino group on the Lysine side chain of the target protein; however it is unable to form multi-chain species (Bayer et al., 1998; Mahajan et al., 1997; Mahajan et al., 1998). SUMO-1 targets substrates including RanGAP1, PML, Sp100, HSF1, Smad4, IκBα, c-Jun, p53 and Mdm2 (Melchior. 2000). RanGAP1, a Ran GTPase-activating is a major SUMO-1 substrate protein involved in nucleocytoplasmic trafficking (Swaminathan et al., 2004). SUMO-1 covalently modifies a single lysine residue at position 526 in the C-terminus of RanGAP1 (Mahajan et al., 1997; Matunis et al., 1996; Muller et al., 1998). SUMO-1 modified RanGAP1 has been found tightly associated with the nuclear envelope (Mahajan et al., 1997; Matunis et al., 1996) an observation which supports its role in nucleocytoplasmic trafficking.

References:

Bayer P, Arndt A, Metzger S, Mahajan R, Melchior F, Jaenicke R, Becker J (1998) Structure determination of the small ubiquitin-related modifier SUMO-1. J Mol Biol 280, 275-86.

Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PS (1996) PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia. Oncogene 13, 971-82.

Kamitani T, Nguyen HP, Yeh ET (1997) Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem 272, 14001-4.

Mahajan R, Delphin C, Guan T, Gerace L, Melchior F (1997) A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88, 97-107.

Mahajan R, Gerace L, Melchior F (1998) Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. J Cell Biol 140, 259-70.

Matunis MJ, Coutavas E, Blobel G (1996) A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J Cell Biol 135, 1457-70.

Melchior F (2000) SUMO–nonclassical ubiquitin. Annu Rev Cell Dev Biol 16, 591-626.

Ubiquigent Limited is a specialist developer and supplier of Drug Discovery Services, high quality Research Tools and Chemistry to the life science research community worldwide.

Ubiquigent’s scientific and business interests have a clear focus; namely the ubiquitin, ubiquitin-like, and integrated signalling systems.

The Company has established its scientific and business credentials with both academic researchers undertaking fundamental scientific discovery and pharmaceutical and biotechnology company scientists exploring the potential of ubiquitin cascade-focused drug discovery.

Ubiquigent benefits from high calibre backing including from private US investors, the UK Medical Research Council, and the University of Dundee. The Company’s headquarters and laboratory operations are based in the UK and are located in a state-of-the-art facility adjacent to the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee (both founded by Professor Sir Philip Cohen). In addition to Ubiquigent’s own facilities and capabilities, such proximity provides ready access to a huge range of additional scientific expertise (1,000+ life-science researchers on site), technological competencies, and assay and analytical platforms.

Ubiquigent staff have a wealth of scientific experience, technological competencies and commercial expertise, gained from within academia, the life science research reagents and services sector, and the pharmaceutical industry, that enables the Company to offer a level of understanding and service to its customers and clients worldwide that few companies may match.