Sumoylation: A Regulatory Protein Modification in Health and Disease

Abstract

Posttranslational modification with small ubiquitin-related modifier (SUMO) proteins is now established as one of the key regulatory protein modifications in eukaryotic cells. Hundreds of proteins involved in processes such as chromatin organization, transcription, DNA repair, macromolecular assembly, protein homeostasis, trafficking, and signal transduction are subject to reversible sumoylation. Hence, it is not surprising that disease links are beginning to emerge and that interference with sumoylation is being considered for intervention. Here, we summarize basic mechanisms and highlight recent developments in the physiology of sumoylation.

Zinc-binding Domain-dependent, Deaminase-independent Actions of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide 2 (Apobec2), Mediate Its Effect on Zebrafish Retina Regeneration

“…shown to regulate a number of processes, including protein subcellular localization, function, and stability (40). To determine whether the N-terminal sumoylation of Apobec2 proteins regulates their subcellular localization, HEK293 cells were transfected with constructs encoding non-sumoylated and sumoylated GFP-tagged (C-terminal) Apobec2 proteins.…”

Ubc9 Is Required for Positive Selection and Late-Stage Maturation of Thymocytes

“…UBC9-mediated SUMOylation is intrinsically involved in cell cycle progression in proliferating cells (34). To investigate whether Ubc9 deficiency affects the acquisition of proliferation competence when T cells immigrate to the periphery, we labeled sorted CD4 SP and CD8 SP cells with CellTrace Violet and stimulated them with anti-CD3 and anti-CD28 for 3 d. Compared with WT cells, Ubc9-deficient SP cells exhibited significantly impaired proliferation driven by TCR signals (Fig.…”

SUMO1‐conjugation is altered during normal aging but not by increased amyloid burden

“…In mammals, three SUMO paralogues can be attached to a target. They are classified into two groups, SUMO1 and SUMO2/3, not only based on their sequence homology but also based on other criteria such as their ability to form chains, their expression levels, and their response to stress (Flotho & Melchior, 2013; Nayak & Muller, 2014). Specifically, in contrast to SUMO2/3, SUMO1 is rarely found as a free moiety in cells.…”

“…Specifically, in contrast to SUMO2/3, SUMO1 is rarely found as a free moiety in cells. SUMOylation is essential for proper cell growth, function, and signaling, and the cycle of SUMOylation/de‐SUMOylation is highly dynamic and sensitive to multiple regulatory and environmental influences (Chymkowitch, Nguea & Enserink, 2015; Eifler & Vertegaal, 2015; Flotho & Melchior, 2013). SUMO substrates are classically found in the cell nucleus where they regulate various processes such as transcription, DNA replication and repair, chromatin organization, splicing, and ribosome assembly (Chymkowitch et al., 2015; Hendriks et al., 2017).…”

“…Moreover, in extranuclear compartments, SUMOylation has been proposed to regulate enzymatic activity, ion channel activity, signaling by G protein‐coupled receptors, mitochondrial dynamics, and various cytoskeletal proteins (Alonso et al., 2015; Andreou & Tavernarakis, 2009). Finally, SUMOylation can affect protein stability or localization and is able to change protein–protein interactions, thus regulating the assembly or disassembly of protein complexes (Chymkowitch et al., 2015; Eifler & Vertegaal, 2015; Flotho & Melchior, 2013). For example, the GTPase‐activating protein RanGAP1, which is the most abundant SUMO1 target in cells, relocalizes to the nuclear envelope upon SUMO1 conjugation where it regulates nuclear trafficking (Mahajan, Delphin, Guan, Gerace & Melchior, 1997; Ritterhoff et al., 2016).…”