Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.

ABSTRACT: Proteins of the small ubiquitin-related modifier (SUMO) family are conjugated to proteins to regulate such cellular processes as nuclear transport, transcription, chromosome segregation and DNA repair. Recently, numerous insights into regulatory mechanisms of the SUMO modification pathway have emerged. Although SUMO-conjugating enzymes can discriminate between SUMO targets, many substrates possess characteristics that facilitate their modification. Other post-translational modifications also regulate SUMO conjugation, suggesting that SUMO signalling is integrated with other signal transduction pathways. A better understanding of SUMO regulatory mechanisms will lead to improved approaches for analysing the function of SUMO and substrate conjugation in distinct cellular pathways.

SUBMITTER: Gareau JR

PROVIDER: S-EPMC3079294 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.

Gareau Jaclyn R JR Lima Christopher D CD

Nature reviews. Molecular cell biology 20101201 12

Proteins of the small ubiquitin-related modifier (SUMO) family are conjugated to proteins to regulate such cellular processes as nuclear transport, transcription, chromosome segregation and DNA repair. Recently, numerous insights into regulatory mechanisms of the SUMO modification pathway have emerged. Although SUMO-conjugating enzymes can discriminate between SUMO targets, many substrates possess characteristics that facilitate their modification. Other post-translational modifications also reg ...[more]

PMID: 21102611

Similar Datasets

Alternative allosteric mechanisms can regulate the substrate and E2 in SUMO conjugation.

Project description:Sumoylation is the covalent attachment of small ubiquitin-like modifier (SUMO) to a target protein. Similar to other ubiquitin-like pathways, three enzyme types are involved that act in succession: an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). To date, unlike other ubiquitin-like mechanisms, sumoylation of the target RanGAP1 (Target(RanGAP1)) does not absolutely require the E3 of the system, RanBP2 (E3(RanBP2)), since the presence of E2 (E2(Ubc9)) is enough to sumoylate Target(RanGAP1). However, in the presence of E3, sumoylation is more efficient. To understand the role of the target specificity of E3(RanBP2) and E2(Ubc9), we carried out molecular dynamics simulations for the structure of E2(Ubc9)-SUMO-Target(RanGAP1) with and without the E3(RanBP2) ligase. Analysis of the dynamics of E2(Ubc9)-SUMO-Target(RanGAP1) in the absence and presence of E3(RanBP2) revealed that two different allosteric sites regulate the ligase activity: (i) in the presence of E3(RanBP2), the E2(Ubc9)'s loop 2; (ii) in the absence of E3(RanBP2), the Leu65-Arg70 region of SUMO. These results provide a first insight into the question of how E3(RanBP2) can act as an intrinsic E3 for E2(Ubc9) and why, in its absence, the activity of E2(Ubc9)-SUMO-Target(RanGAP1) could still be maintained, albeit at lower efficiency.

| S-EPMC7398049 | biostudies-literature

SUMO Conjugation to BZR1 Enables Brassinosteroid Signaling to Integrate Environmental Cues to Shape Plant Growth.

Project description:Brassinosteroids (BRs) play crucial roles in plant development, but little is known of mechanisms that integrate environmental cues into BR signaling. Conjugation to the small ubiquitin-like modifier (SUMO) is emerging as an important mechanism to transduce environmental cues into cellular signaling. In this study, we show that SUMOylation of BZR1, a key transcription factor of BR signaling, provides a conduit for environmental influence to modulate growth during stress. SUMOylation stabilizes BZR1 in the nucleus by inhibiting its interaction with BIN2 kinase. During salt stress, Arabidopsis plants arrest growth through deSUMOylation of BZR1 in the cytoplasm by promoting the accumulation of the BZR1 targeting SUMO protease, ULP1a. ULP1a mutants are salt tolerant and insensitive to the BR inhibitor, brassinazole. BR treatment stimulates ULP1a degradation, allowing SUMOylated BZR1 to accumulate and promote growth. This study uncovers a mechanism for integrating environmental cues into BR signaling to shape growth.

| S-EPMC7181186 | biostudies-literature

SUMO conjugation regulates immune signalling.

Project description:Post-translational modifications (PTMs) are critical drivers and attenuators for proteins that regulate immune signalling cascades in host defence. In this review, we explore functional roles for one such PTM, the small ubiquitin-like modifier (SUMO). Very few of the SUMO conjugation targets identified by proteomic studies have been validated in terms of their roles in host defence. Here, we compare and contrast potential SUMO substrate proteins in immune signalling for flies and mammals, with an emphasis on NFκB pathways. We discuss, using the few mechanistic studies that exist for validated targets, the effect of SUMO conjugation on signalling and also explore current molecular models that explain regulation by SUMO. We also discuss in detail roles of evolutionary conservation of mechanisms, SUMO interaction motifs, crosstalk of SUMO with other PTMs, emerging concepts such as group SUMOylation and finally, the potentially transforming roles for genome-editing technologies in studying the effect of PTMs.

| S-EPMC7714519 | biostudies-literature

SUMO conjugation to the pattern recognition receptor FLS2 triggers intracellular signalling in plant innate immunity.

Project description:Detection of conserved microbial patterns by host cell surface pattern recognition receptors (PRRs) activates innate immunity. The FLAGELLIN-SENSITIVE 2 (FLS2) receptor perceives bacterial flagellin and recruits another PRR, BAK1 and the cytoplasmic-kinase BIK1 to form an active co-receptor complex that initiates antibacterial immunity in Arabidopsis. Molecular mechanisms that transmit flagellin perception from the plasma-membrane FLS2-associated receptor complex to intracellular events are less well understood. Here, we show that flagellin induces the conjugation of the SMALL UBIQUITIN-LIKE MODIFIER (SUMO) protein to FLS2 to trigger release of BIK1. Disruption of FLS2 SUMOylation can abolish immune responses, resulting in susceptibility to bacterial pathogens in Arabidopsis. We also identify the molecular machinery that regulates FLS2 SUMOylation and demonstrate a role for the deSUMOylating enzyme, Desi3a in innate immunity. Flagellin induces the degradation of Desi3a and enhances FLS2 SUMOylation to promote BIK1 dissociation and trigger intracellular immune signalling.

| S-EPMC6281677 | biostudies-literature

Regulation of USP28 deubiquitinating activity by SUMO conjugation.

Project description:USP28 (ubiquitin-specific protease 28) is a deubiquitinating enzyme that has been implicated in the DNA damage response, the regulation of Myc signaling, and cancer progression. The half-life stability of major regulators of critical cellular pathways depends on the activities of specific ubiquitin E3 ligases that target them for proteosomal degradation and deubiquitinating enzymes that promote their stabilization. One function of the post-translational small ubiquitin modifier (SUMO) is the regulation of enzymatic activity of protein targets. In this work, we demonstrate that the SUMO modification of the N-terminal domain of USP28 negatively regulates its deubiquitinating activity, revealing a role for the N-terminal region as a regulatory module in the control of USP28 activity. Despite the presence of ubiquitin-binding domains in the N-terminal domain, its truncation does not impair deubiquitinating activity on diubiquitin or polyubiquitin chain substrates. In contrast to other characterized USP deubiquitinases, our results indicate that USP28 has a chain preference activity for Lys(11), Lys(48), and Lys(63) diubiquitin linkages.

| S-EPMC4263883 | biostudies-literature

Identification of biochemically distinct properties of the small ubiquitin-related modifier (SUMO) conjugation pathway in Plasmodium falciparum.

Project description:Small ubiquitin-related modifiers (SUMOs) are post-translationally conjugated to other proteins and are thereby essential regulators of a wide range of cellular processes. Sumoylation, and enzymes of the sumoylation pathway, are conserved in the malaria causing parasite, Plasmodium falciparum. However, the specific functions of sumoylation in P. falciparum, and the degree of functional conservation between enzymes of the human and P. falciparum sumoylation pathways, have not been characterized. Here, we demonstrate that sumoylation levels peak during midstages of the intra-erythrocyte developmental cycle, concomitant with hemoglobin consumption and elevated oxidative stress. In vitro studies revealed that P. falciparum E1- and E2-conjugating enzymes interact effectively to recognize and modify RanGAP1, a model mammalian SUMO substrate. However, in heterologous reactions, P. falciparum E1 and E2 enzymes failed to interact with cognate human E2 and E1 partners, respectively, to modify RanGAP1. Structural analysis, binding studies, and functional assays revealed divergent amino acid residues within the E1-E2 binding interface that define organism-specific enzyme interactions. Our studies identify sumoylation as a potentially important regulator of oxidative stress response during the P. falciparum intra-erythrocyte developmental cycle, and define E1 and E2 interactions as a promising target for development of parasite-specific inhibitors of sumoylation and parasite replication.

| S-EPMC3784690 | biostudies-literature

SUMO conjugation to the pattern recognition receptor FLS2 triggers intracellular signalling in plant innate immunity

Project description:Arabidopsis lines expressing 35S::Strep-SUMO1H89R in Col-0 background were generated since the H89R SUMO1 variant simplifies MS/MS detection of SUMO conjugated lysines after trypsinization (Miller et al., 2010). Transgenic seedlings were treated with water or 250nM flg22 for 30 minutes and total protein extracts including membrane fractions were affinity purified with Pierce™ Streptavidin Magnetic Beads. LC-MS analysis of eluting proteins allowed identification of candidate SUMO-conjugated proteins in response to flg22 treatment.

2019-11-12 | PXD011552 | Pride

System-wide identification of wild-type SUMO-2 conjugation sites.

Project description:SUMOylation is a reversible post-translational modification (PTM) regulating all nuclear processes. Identification of SUMOylation sites by mass spectrometry (MS) has been hampered by bulky tryptic fragments, which thus far necessitated the use of mutated SUMO. Here we present a SUMO-specific protease-based methodology which circumvents this problem, dubbed Protease-Reliant Identification of SUMO Modification (PRISM). PRISM allows for detection of SUMOylated proteins as well as identification of specific sites of SUMOylation while using wild-type SUMO. The method is generic and could be widely applied to study lysine PTMs. We employ PRISM in combination with high-resolution MS to identify SUMOylation sites from HeLa cells under standard growth conditions and in response to heat shock. We identified 751 wild-type SUMOylation sites on endogenous proteins, including 200 dynamic SUMO sites in response to heat shock. Thus, we have developed a method capable of quantitatively studying wild-type mammalian SUMO at the site-specific and system-wide level.

| S-EPMC4490555 | biostudies-literature

Identification of SUMO conjugation sites in the budding yeast proteome.

Project description:Post-translational modification by the small ubiquitin-like modifier (SUMO) is an important mechanism regulating protein function. Identification of SUMO conjugation sites on substrates is a challenging task. Here we employed a proteomic method to map SUMO acceptor lysines in budding yeast proteins. We report the identification of 257 lysine residues where SUMO is potentially attached. Amongst the hits, we identified already known SUMO substrates and sites, confirming the success of the approach. In addition, we tested several of the novel substrates using SUMO immunoprecipitation analysis and confirmed that the SUMO acceptor lysines identified in these proteins are indeed bona fide SUMOylation sites. We believe that the collection of SUMO sites presented here is an important resource for future functional studies of SUMOylation in yeast.

| S-EPMC5657824 | biostudies-literature

Molecular mechanisms of substrate recognition and specificity of New Delhi metallo-?-lactamase.

Project description:Carbapenems are one of the last lines of defense for Gram-negative pathogens, such as members of the Enterobacteriaceae. Despite the fact that most carbapenems are resistant to extended-spectrum ?-lactamase (ESBL), emerging metallo-?-lactamases (MBLs), including New Delhi metallo-?-lactamase 1 (NDM-1), that can hydrolyze carbapenems have become prevalent and are frequently associated with the so-called "superbugs," for which treatments are extremely limited. Crystallographic study sheds light on the modes of antibiotic binding to NDM-1, yet the mechanisms governing substrate recognition and specificity are largely unclear. This study provides a connection between crystallographic study and the functional significance of NDM-1, with an emphasis on the substrate specificity and catalysis of various ?-lactams. L1 loop residues L59, V67, and W87 were important for the activity of NDM-1, most likely through maintaining the partial folding of the L1 loop or active site conformation through hydrophobic interaction with the R groups of ?-lactams or the ?-lactam ring. Substitution of alanine for L59 showed greater reduction of MICs to ampicillin and selected cephalosporins, whereas substitutions of alanine for V67 had more impact on the MICs of carbapenems. K224 and N233 on the L3 loop played important roles in the recognition of substrate and contributed to substrate hydrolysis. These data together with the structure comparison of the B1 and B2 subclasses of MBLs revealed that the broad substrate specificity of NDM-1 could be due to the ability of its wide active site cavity to accommodate a wide range of ?-lactams. This study provides insights into the development of efficient inhibitors for NDM-1 and offers an efficient tactic with which to study the substrate specificities of other ?-lactamases.

| S-EPMC4135836 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data