SUMO chains: polymeric signals

2010 ◽  
Vol 38 (1) ◽  
pp. 46-49 ◽  
Author(s):  
Alfred C.O. Vertegaal
Keyword(s):  
Ring Finger ◽  
Dependent Manner ◽  
Ring Finger Protein ◽  
Synthetic Lethal ◽  
Target Proteins ◽  
Sumo Proteases ◽  
Lysine Residues ◽  
Chain Synthesis ◽  
A Chain ◽  
Mitosis And Meiosis

Ubiquitin and ubiquitin-like proteins are conjugated to a wide variety of target proteins that play roles in all biological processes. Target proteins are conjugated to ubiquitin monomers or to ubiquitin polymers that form via all seven internal lysine residues of ubiquitin. The fate of these target proteins is controlled in a chain architecture-dependent manner. SUMO (small ubiquitin-related modifier) shares the ability of ubiquitin to form chains via internal SUMOylation sites. Interestingly, a SUMO-binding site in Ubc9 is important for SUMO chain synthesis. Similar to ubiquitin–polymer cleavage by USPs (ubiquitin-specific proteases), SUMO chain formation is reversible. SUMO polymers are cleaved by the SUMO proteases SENP6 [SUMO/sentrin/SMT3 (suppressor of mif two 3)-specific peptidase 6], SENP7 and Ulp2 (ubiquitin-like protease 2). SUMO chain-binding proteins including ZIP1, SLX5/8 (synthetic lethal of unknown function 5/8), RNF4 (RING finger protein 4) and CENP-E (centromere-associated protein E) have been identified that interact non-covalently with SUMO chains, thereby regulating target proteins that are conjugated to SUMO multimers. SUMO chains play roles in replication, in the turnover of SUMO targets by the proteasome and during mitosis and meiosis. Thus signalling via polymers is an exciting feature of the SUMO family.

Molecular Functions of Rice Cytosol-Localized RING Finger Protein 1 in Response to Salt and Drought and Comparative Analysis of Its Grass Orthologs

2019 ◽  
Vol 60 (11) ◽  
pp. 2394-2409 ◽  
Author(s):  
Yong Chan Park ◽  
Seung Young Choi ◽  
Jong Ho Kim ◽  
Cheol Seong Jang
Keyword(s):  
Higher Plants ◽  
Ring Finger ◽  
E3 Ligase ◽  
26S Proteasome ◽  
Dependent Manner ◽  
Ring Finger Protein ◽  
Target Proteins ◽  
Finger Protein ◽  
Molecular Functions ◽  
Salt And Drought Stresses

Abstract In higher plants, the post-translational modification of target proteins via the attachment of molecules such as ubiquitin (Ub) mediates a variety of cellular functions via the Ub/26S proteasome system. Here, a really interesting new gene (RING)-H2 type E3 ligase, which regulates target proteins via the Ub/26S proteasome system, was isolated from a rice plant, and its other grass orthologs were examined to determine the evolution of its molecular function during speciation. The gene encoding Oryza sativa cytoplasmic-localized RING finger protein 1 (OsCLR1) was highly expressed under salt and drought stresses. By contrast, the three grass orthologs, SbCLR1 from Sorghum bicolor, ZmCLR1 from Zea mays and TaCLR1 from Triticum aestivum, showed different responses to these stresses. Despite these differences, all four orthologs exhibited E3 ligase activity with cytosol-targeted localization, demonstrating conserved molecular functions. Although OsCLR1-overexpressing plants showed higher survival rates under both salt and drought stresses than that of the wild type (WT) plants, this pattern was not observed in the other orthologs. In addition, OsCLR1-overexpressing plants exhibited lower germination rates in ABA than that of WT plants, whereas the three ortholog CLR1-overexpressing plants showed rates similar to the WT plants. These results indicate the positive regulation of OsCLR1 in response to salt and drought in an ABA-dependent manner. Despite the molecular functions of the three CLR1 orthologs remaining largely unknown, our results provide an insight into the evolutionary fate of CLR1 grass orthologs during speciation after the divergence from a common ancestor.

scholarly journals Regulation of p27 Degradation and S-Phase Progression by Ro52 RING Finger Protein

2006 ◽  
Vol 26 (16) ◽  
pp. 5994-6004 ◽  
Author(s):  
Abdelmajid Sabile ◽  
Andrea Michael Meyer ◽  
Christiane Wirbelauer ◽  
Daniel Hess ◽  
Ulrike Kogel ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Kinase Inhibitor ◽  
Ring Finger ◽  
E3 Ligase ◽  
S Phase ◽  
Dependent Manner ◽  
Ring Finger Protein ◽  
Catalytic Core ◽  
Finger Protein ◽  
Phase Progression

ABSTRACT Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle. According to a current model, the ubiquitination of p27 during S-phase progression is mediated by SCFSkp2 E3 ligase that captures Thr187-phosphorylated p27 by means of the F-box protein Skp2, which in turn couples the bound substrate via Skp1 to a catalytic core complex composed of Cul1 and the Rbx/Roc RING finger protein. Here we identify Skp2 as a component of an Skp1-cullin-F-box complex that is based on a Cul1-Ro52 RING finger B-box coiled-coil motif family protein catalytic core. Ro52-containing complexes display E3 ligase activity and promote the ubiquitination of Thr187-phosphorylated p27 in a RING-dependent manner in vitro. The knockdown of Ro52 expression in human cells with small interfering RNAs causes the accumulation of p27 and the failure of cells to enter S phase. Importantly, these effects are abrogated by the simultaneous removal of p27. Taken together, these data suggest a key role for Ro52 RING finger protein in the regulation of p27 degradation and S-phase progression in mammalian cells and provide evidence for the existence of a Cul1-based catalytic core that utilizes Ro52 RING protein to promote ubiquitination.

scholarly journals Development of a High-Throughput Screening Assay for Inhibitors of Small Ubiquitin-Like Modifier Proteases

2013 ◽  
Vol 18 (5) ◽  
pp. 621-628 ◽  
Author(s):  
Wei Yang ◽  
Liangli Wang ◽  
Wulf Paschen
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Dependent Manner ◽  
Screening Assay ◽  
Sumo Protease ◽  
Sumo Conjugation ◽  
Sumo Proteases ◽  
High Throughput Screening Assay ◽  
Lysine Residues ◽  
Protease Substrate

Small ubiquitin-like modifier (SUMO1–3) is a small group of proteins that are ligated to lysine residues in target proteins. SUMO conjugation is a highly dynamic process, as SUMOylated proteins are rapidly deconjugated by SUMO proteases. SUMO conjugation/deconjugation plays pivotal roles in major cellular pathways and is associated with a number of pathological conditions. It is therefore of significant clinical interest to develop new strategies to screen for compounds to specifically interfere with SUMO conjugation/deconjugation. Here, we describe a novel high-throughput screening (HTS)–compatible assay to identify inhibitors of SUMO proteases. The assay is based on AlphaScreen technology and uses His-tagged SUMO2 conjugated to Strep-tagged SUMO3 as a SUMO protease substrate. A bacterial SUMOylation system was used to generate this substrate. A three-step purification strategy was employed to yield substrate of high quality. Our data indicated that this unique substrate can be readily detected in the AlphaScreen assays in a dose-dependent manner. Cleavage reactions by SUMO protease with or without inhibitor were monitored based on AlphaScreen signals. Furthermore, the assay was adapted to a 384-well format, and the interplate and interday variability was evaluated in eight 384-well plates. The average Z′ factor was 0.83 ± 0.04, confirming the suitability for HTS applications.

scholarly journals The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Oncogenesis ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Le Shi ◽  
Dongyue Du ◽  
Yunhua Peng ◽  
Jiankang Liu ◽  
Jiangang Long
Keyword(s):  
Ring Finger ◽  
Tumor Promotion ◽  
Dependent Manner ◽  
Ring Finger Protein ◽  
E3 Ligases ◽  
Finger Protein ◽  
Novel Complex ◽  
Cullin 7 ◽  
Potential Use

Abstract Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.

scholarly journals PIAS1 potentiates the anti-EBV activity of SAMHD1 through SUMOylation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Farjana Saiada ◽  
Kun Zhang ◽  
Renfeng Li
Keyword(s):  
Lytic Replication ◽  
Dependent Manner ◽  
Dna Viruses ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Barr Virus ◽  
Sumo Ligase ◽  
Lysine Residues ◽  
Epstein Barr ◽  
Rna And Dna

Abstract Background Sterile alpha motif and HD domain 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that restricts the infection of a variety of RNA and DNA viruses, including herpesviruses. The anti-viral function of SAMHD1 is associated with its dNTPase activity, which is regulated by several post-translational modifications, including phosphorylation, acetylation and ubiquitination. Our recent studies also demonstrated that the E3 SUMO ligase PIAS1 functions as an Epstein-Barr virus (EBV) restriction factor. However, whether SAMHD1 is regulated by PIAS1 to restrict EBV replication remains unknown. Results In this study, we showed that PIAS1 interacts with SAMHD1 and promotes its SUMOylation. We identified three lysine residues (K469, K595 and K622) located on the surface of SAMHD1 as the major SUMOylation sites. We demonstrated that phosphorylated SAMHD1 can be SUMOylated by PIAS1 and SUMOylated SAMHD1 can also be phosphorylated by viral protein kinases. We showed that SUMOylation-deficient SAMHD1 loses its anti-EBV activity. Furthermore, we demonstrated that SAMHD1 is associated with EBV genome in a PIAS1-dependent manner. Conclusion Our study reveals that PIAS1 synergizes with SAMHD1 to inhibit EBV lytic replication through protein–protein interaction and SUMOylation.

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