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SUMO E3 ligases SUMOylate target proteins

SUMO proteins are conjugated to lysine residues of target proteins via an isopeptide bond with the C-terminal glycine of SUMO (reviewed in Zhao 2007, Gareau and Lima 2010, Hannoun et al. 2010, Citro and Chiocca 2013, Yang and Chiang 2013). Proteomic analyses indicate that SUMO is conjugated to hundreds of proteins and most targets of SUMOylation are nuclear (Vertegal et al. 2006, Bruderer et al. 2011, Tatham et al. 2011, Da Silva et al. 2012, Becker et al. 2013).UBE2I (UBC9), the E2 activating enzyme of the SUMO pathway, is itself also a SUMO E3 ligase. Most SUMOylation reactions will proceed with only the substrate protein and the UBE2I:SUMO thioester conjugate. The rates of some reactions are further enhanced by the action of other E3 ligases such as RANBP2. These E3 ligases catalyze SUMO transfer to substrate by one of two basic mechanisms: they interact with both the substrate and UBE2I:SUMO thus bringing them into proximity or they enhance the release of SUMO from UBE2I to the substrate.Most SUMOylation reactions occur in the nucleoplasm therefore most targets of SUMOylation are nuclear proteins such as transcription factors, transcription cofactors, and nuclear receptors. In the cell SUMO1 is mainly concentrated at the nuclear membrane and in nuclear bodies. Most SUMO1 is conjugated to RANGAP1 near the nuclear pore. SUMO2 is at least partially cytosolic and SUMO3 is located mainly in nuclear bodies. Most SUMO2 and SUMO3 is unconjugated in unstressed cells and becomes conjugated to target proteins in response to stress (Golebiowski et al. 2009). Especially notable is the requirement for recruitment of SUMO to sites of DNA damage where conjugation to targets seems to coordinate the repair process (Flotho and Melchior 2013).Several effects of SUMOylation have been described: steric interference with protein-protein interactions, interference with other post-translational modifications such as ubiquitinylation and phosphorylation, and recruitment of proteins that possess a SUMO-interacting motif (SIM) (reviewed in Zhao 2007, Flotho and Melchior 2013, Jentsch and Psakhye 2013, Yang and Chiang 2013). In most cases SUMOylation inhibits the activity of the target protein.The SUMOylation reactions included in this module have met two criteria: They have been verified by assays of individual proteins (as opposed to mass proteomic assays) and the effect of SUMOylation on the function of the target protein has been tested.

from REACTOME source record: R-HSA-3108232
Type: pathway
Taxonomic scope
organism-specific biosystem
Homo sapiens

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