SUMO PATHWAY

Structural and functional studies on the SUMO modification Pathway

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 Obiettivo del progetto (Objective)

'The Small Ubiquitin-related MOdifier (SUMO) belongs to a family of proteins that become covalently attached to other proteins as post-translational modifications. Proteins that are modified by SUMO participate in diverse cellular processes, including transcriptional regulation, nuclear transport, maintenance of genome integrity, and signal transduction. Conjugation (or modification) by SUMO is controlled by an enzyme pathway analogous to the ubiquitin pathway. The functional consequences of SUMO attachment vary greatly from substrate to substrate. Frequently, SUMO alters interactions of substrates with other proteins or with DNA, but SUMO can also act by blocking ubiquitin attachment sites. An unusual feature of SUMO modification is that only a small fraction of the substrate is sumoylated at any given time, so the consequences of conjugation are not proportionate to such small fraction of modified substrates. Control of SUMO conjugation seems to be a dynamic process of conjugation by SUMO E3 ligase and deconjugation by SUMO isopeptidases. There are many aspects of the SUMO pathway that are still not very well understood. For instance, a few number of SUMO E3 ligases have been reported despite the high number of substrates modified by SUMO, and it is not clear how those known SUMO E3s ligases work. Additionally, even though the emerging role of non-covalent protein-protein interaction by the SUMO binding motifs (SBM) in the regulation of several SUMO modification outcomes, only few bona fide examples have been reported so far. Finally, biochemical and bioinformatic approaches have identified in mammals several members of the SUMO Ulp/Senp protease family.The precise physiological role for SUMO proteases is still relatively unclear, although recent reports support the hypothesis that Senp family members participate in non-redundant cellular functions and that these proteases are regulated by cellular localization dictated by their non-homologous N-terminal domain.'

Introduzione (Teaser)

Considerable progress has been made during the SUMO Pathway project to improve our knowledge of the inner workings of the cells that make up the human body.

Descrizione progetto (Article)

SUMO is the acronym for the small ubiquitin-related modifier, a special protein that can modify several other proteins that participate in important cellular processes like nuclear transport.

European funding has been allocated to the 'Structural and functional studies on the SUMO modification pathway' (SUMO Pathway) project to study the SUMO modification pathway. X-ray crystallography has been employed to help understand how SUMO conjugates with E3 ligases. This has enabled the characterisation of the corresponding SUMO binding motif for the RNF4 E3 ligase.

The strength of several members of the SUMO protease family in deconjugating SUMO is also being rated. Of particular interest is the ability of SENP6 and SENP7 to distinguish between different types of SUMO, known as isoforms. In fact, it has been possible to manipulate protease activity, either increasing or decreasing it, with the aid of special substrates. These experiments are being extended to bacteria and other micro-organisms in the laboratory.

The SUMO Pathway results are being shared with the research community through publications in peer-reviewed scientific journals.