A fly view of a SUMO-targeted ubiquitin ligase

Abstract

Posttranscriptional modifications of proteins by the ubiquitin and SUMO (Small Ubiquitin-related Modifier) pathways regulate the function of protein networks, enable cells to respond to signaling cues during development, and to cope with the changing environment during adult life. Both modifications can impact protein stability, localization, protein-protein interactions and/or function. While both pathways have been well studied individually, the long-speculated nature of crosstalk between SUMO and ubiquitin pathways has been molecularly enigmatic. Recent work in yeast and mammalian cells identified the connection between the two pathways in the form of a conserved family of RING finger ubiquitin ligases termed SUMO-Targeted ubiquitin ligases (STUbLs). These proteins bind to SUMOylated substrates via their SUMO interaction motif and subsequently target them for ubiquitylation. Characterization of Degringolade (Dgrn), a STUbL gene in the fly genome, enabled us to evaluate the contribution of STUbLs to the development of multi-cellular organisms. Analysis of dgrn mutants showed that they are required for cyto-nuclear organization during early embryonic development, and are likely required to cope with mitotic stress and DNA damage. Furthermore, in transcription, STUbLs regulate protein-protein interactions, and are part of molecular machinery that regulates co-repressor choice and gene-expression selectivity during development.

The SUMO Pathway Promotes Basic Helix-Loop-Helix Proneural Factor Activity via a Direct Effect on the Zn Finger Protein Senseless

“…It is therefore interesting that another role for SUMOylation in SOP specification has recently been identified in relation to HES repressors. A model has been proposed in which the repressive activity of HES proteins during neurogenesis (as well as segmentation and sex determination) is disrupted by the SUMO-targeted ubiquitin ligase (STUbL) Degringolade (DGRN) (1,2,5). DGRN binds to SUMOylated Groucho (GRO), the corepressor of HES.…”

Regulation of Protein-Protein Interactions by the SUMO and Ubiquitin Pathways

“…SUMO conjugation of target proteins results in a change in their activity, affecting protein localization, and modulates composition of protein complexes. In some cases SUMOylation may act as a priming modification that promotes ubiquitylation via a specific specialized sub-type of E3 ubiquitin ligases termed SUMO-Targeted Ubiquitin Ligases (Abed et al, 2011b;Praefcke et al, 2011). Within the scope of this chapter we will focus solely on the interactions mediated by ubiquitin and SUMO.…”

“…A first direct and enzymatic link between the two pathways was established by the identification of SUMO-targeted ubiquitin ligases (STUbLs). STUbLs are a unique group of RING proteins: they bind non-covalently to the SUMO moiety of SUMOylated proteins via several SIM motifs, and subsequently target the SUMOylated protein for ubiquitylation via a RING domain [Sun et al, 2007;Geoffroy &Hay, 2009;Abed et al 2011b]. STUbLs impact protein stability, localization, and are required for the maintenance of genomic integrity, transcription and are involved cancer.…”

“…Yet, no clear STUbL orthologs exist in the worm C. elegans. These members are structurally and functionally conserved, as RNF4 protein can substitute for the yeast and fly genes in functional assays (Abed et al, 2011aAbed et al, 2011bBarry et al, 2011;Praefcke et al, 2011). Recent structural work from the Hay lab uncovered that RNF4, and likely other STUbLs, function as dimers and that dimer formation is actively required to facilitate SUMO-dependent ubiquitin conjugation (Plechanovova' et al 2011).…”

Study of Synergy between Mentha pulegium Essential Oil, Honey and Bacteriocin-like Inhibitory Substance E204 against Listeria monocytogenes CECT 4032 and Escherichia coli K12

“…In recent years, essential oils have shown powerful biological properties such as antimicrobial activity (Kamazeri et al, 2012) and antioxidant activity (Gardeli et al, 2008;Abed et al, 2011;Aidi Wannes et al, 2010). However, the activity of the essential oil in combination with other agents is poorly reported.…”