SUMO E3 ligases SUMOylate target proteins

Stable Identifier
R-HSA-3108232
Type
Pathway
Species
Homo sapiens
Compartment
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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). Within the nucleus SUMOylation targets include transcription factors (TFs), transcription cofactors (TCs), intracellular (nuclear) receptors, RNA binding proteins, RNA splicing proteins, polyadenylation proteins, chromatin organization proteins, DNA replication proteins, DNA methylation proteins, DNA damage response and repair proteins, immune response proteins, SUMOylation proteins, and ubiquitinylation proteins. Mitochondrial fission proteins are SUMOylated at the mitochondrial outer membrane.
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.
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.

Literature References
PubMed ID Title Journal Year
20674646 Post-translational modification by SUMO

Hannoun, Z, Greenhough, S, Jaffray, E, Hay, RT, Hay, DC

Toxicology 2010
22811915 Strategies to Identify Recognition Signals and Targets of SUMOylation

Da Silva-Ferrada, E, Lopitz-Otsoa, F, Lang, V, Rodriguez, MS, Matthiesen, R

Biochem Res Int 2012
24273646 Sumoylation in gene regulation, human disease, and therapeutic action

Yang, XJ, Chiang, CM

F1000Prime Rep 2013
23277067 Sumo paralogs: redundancy and divergencies

Citro, S, Chiocca, S

Front Biosci (Schol Ed) 2013
24016193 Control of Nuclear Activities by Substrate-Selective and Protein-Group SUMOylation

Jentsch, S, Psakhye, I

Annu. Rev. Genet. 2013
21102611 The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition

Gareau, JR, Lima, CD

Nat. Rev. Mol. Cell Biol. 2010
19471022 System-wide changes to SUMO modifications in response to heat shock

Golebiowski, F, Matic, I, Tatham, MH, Cole, C, Yin, Y, Nakamura, A, Cox, J, Barton, GJ, Mann, M, Hay, RT

Sci Signal 2009
23746258 Sumoylation: a regulatory protein modification in health and disease

Flotho, A, Melchior, F

Annu. Rev. Biochem. 2013
23503365 Detecting endogenous SUMO targets in mammalian cells and tissues

Becker, J, Barysch, SV, Karaca, S, Dittner, C, Hsiao, HH, Berriel Diaz, M, Herzig, S, Urlaub, H, Melchior, F

Nat. Struct. Mol. Biol. 2013
21693764 Comparative proteomic analysis identifies a role for SUMO in protein quality control

Tatham, MH, Matic, I, Mann, M, Hay, RT

Sci Signal 2011
21252943 Purification and identification of endogenous polySUMO conjugates

Bruderer, R, Tatham, MH, Plechanovova, A, Matic, I, Garg, AK, Hay, RT

EMBO Rep. 2011
17763827 Sumoylation regulates diverse biological processes

Zhao, J

Cell. Mol. Life Sci. 2007
17000644 Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics

Vertegaal, AC, Andersen, JS, Ogg, SC, Hay, RT, Mann, M, Lamond, AI

Mol. Cell Proteomics 2006
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