SUMOhydro: A Novel Method for the Prediction of Sumoylation Sites Based on Hydrophobic Properties

Chen, Yongzi; Chen, Zhe; Gong, Yu Ai; Ying, Guoguang

doi:10.1371/journal.pone.0039195

Cited by 57 publications

(44 citation statements)

References 34 publications

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“…Protein sumoylation couples a glycine residue in the carboxyl terminus of the activated SUMO protein to the ε-amino group of an acceptor lysine in the target protein, resulting in a covalent, but highly labile, isopeptide bond. The majority of known SUMO-acceptor sites in target proteins conform to the sequence ψKx(D/E), where ψ corresponds to an aliphatic, hydrophobic amino acid and “x” can be any amino acid [4,27]. …”

Section: Sumoylationmentioning

confidence: 99%

Regulation of transcription factor activity by interconnected post-translational modifications

Filtz

Vogel

Leid

2014

Trends in Pharmacological Sciences

187

146

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Transcription factors comprise just over 7% of the human proteome and serve as the gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated, cell signaling pathways converge on transcription factors, decorating these proteins with an array of post-translational modifications (PTMs) that are often interdependent, being linked in time, space, and combinatorial function. These PTMs orchestrate every activity of a transcription factor over its entire lifespan—from subcellular localization to protein–protein interactions, sequence-specific DNA binding, transcriptional regulatory activity, and protein stability—and play key roles in the epigenetic regulation of gene expression. The multitude of PTMs of transcription factors also offers numerous potential points of intervention for development of therapeutic agents to treat a wide spectrum of diseases. We review PTMs most commonly targeting transcription factors, focusing on recent reports of sequential and linked PTMs of individual factors.

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Section: Sumoylationmentioning

confidence: 99%

Regulation of transcription factor activity by interconnected post-translational modifications

Filtz

Vogel

Leid

2014

Trends in Pharmacological Sciences

187

146

View full text Add to dashboard Cite

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“…However, tertiary structure undoubtedly has a strong influence on whether a lysine can be efficiently SUMOylated and although some algorithms do incorporate empirical data on local secondary structure, the 3-dimensional environment of the predicted site presents a challenge to SUMO-site prediction that has yet to be met. Nevertheless, several freely available algorithms (PTMProber, 9 JASSA, 10 GPS-SUMO, 11 SUMOhydro, 12 SUMOplot (http://www. abgent.com/sumoplot)) are useful for comparing protein sequences to positively identify SUMOylation targets.…”

Section: Introductionmentioning

confidence: 99%

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

et al. 2017

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The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant. Co-opting this principle to CRMP2, we demonstrate that, of 3 sites predicted to be SUMOylated in CRMP2, only the lysine 374 site is a SUMOylation client. A reduction in NaV1.7 currents was the corollary of the loss of CRMP2 SUMOylation at this site. A 1.78-A -resolution crystal structure of mouse CRMP2 was solved using X-ray crystallography, revealing lysine 374 as buried within the CRMP2 tetramer interface but exposed in the monomer. Since CRMP2 SUMOylation is dependent on phosphorylation, we postulate that this state forces CRMP2 toward a monomer, exposing the SUMO site and consequently, resulting in constitutive regulation of NaV1.7.

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“…Through simultaneous binding of UBC9, its bound SUMO, and the target protein, E3 ligases confer substrate and SUMO paralog specificity. Approximately 75% of SUMO-conjugated lysines are found within type I consensus elements, KX(D/E), where is a large hydrophobic residue and X is any amino acid (35)(36)(37).…”

Section: Gfi1mentioning

confidence: 99%

SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis

Andrade

Velinder

Singer

et al. 2016

Molecular and Cellular Biology

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Cell fate specification requires precise coordination of transcription factors and their regulators to achieve fidelity and flexibility in lineage allocation. The transcriptional repressor growth factor independence 1 (GFI1) is comprised of conserved Snail/Slug/ Gfi1 (SNAG) and zinc finger motifs separated by a linker region poorly conserved with GFI1B, its closest homolog. Moreover, GFI1 and GFI1B coordinate distinct developmental fates in hematopoiesis, suggesting that their functional differences may derive from structures within their linkers. We show a binding interface between the GFI1 linker and the SP-RING domain of PIAS3, an E3-SUMO (small ubiquitin-related modifier) ligase. The PIAS3 binding region in GFI1 contains a conserved type I SUMOylation consensus element, centered on lysine-239 (K239). In silico prediction algorithms identify K239 as the only highprobability site for SUMO modification. We show that GFI1 is modified by SUMO at K239. SUMOylation-resistant derivatives of GFI1 fail to complement Gfi1 depletion phenotypes in zebrafish primitive erythropoiesis and granulocytic differentiation in cultured human cells. LSD1/CoREST recruitment and MYC repression by GFI1 are profoundly impaired for SUMOylation-resistant GFI1 derivatives, while enforced expression of MYC blocks granulocytic differentiation. These findings suggest that SUMOylation within the GFI1 linker favors LSD1/CoREST recruitment and MYC repression to govern hematopoietic differentiation.

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SUMOhydro: A Novel Method for the Prediction of Sumoylation Sites Based on Hydrophobic Properties

Cited by 57 publications

References 34 publications

Regulation of transcription factor activity by interconnected post-translational modifications

Regulation of transcription factor activity by interconnected post-translational modifications

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis

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